Skip to main content
Erschienen in: Immunologic Research 2/2015

01.06.2015 | Interpretive synthesis review article

Association of TLR1, TLR2, TLR4, TLR6, and TIRAP polymorphisms with disease susceptibility

verfasst von: Mamoona Noreen, Muhammad Arshad

Erschienen in: Immunologic Research | Ausgabe 2/2015

Einloggen, um Zugang zu erhalten

Abstract

Toll like receptors (TLRs) play a crucial role in regulation of innate as well as adaptive immunity. TLRs recognize a distinct but limited repertoire of conserved microbial products. Ligand binding to TLRs activates the signaling cascade and results in activation of multiple inflammatory genes. Variation in this immune response is under genetic control. Polymorphisms in genes associated with inflammatory pathway especially influence the outcome of diseases. TLR2 makes heterodimer with TLR1 or TLR6 and recognizes a wide variety of microbial ligands. In this review, we summarize studies of polymorphisms in genes encoding TLR1, TLR2, TLR4, TLR6, and most polymorphic adaptor protein, Mal/TIRAP, revealing their effect on susceptibility to diseases.
Literatur
1.
Zurück zum Zitat Beutler B. Innate immunity: an overview. Mol Immunol. 2004;40(12):845–59.PubMed Beutler B. Innate immunity: an overview. Mol Immunol. 2004;40(12):845–59.PubMed
2.
Zurück zum Zitat Barber RC, Chang LY, Arnoldo BD, Purdue GF, Hunt JL, Horton JW, et al. Innate immunity SNPs are associated with risk for severe sepsis after burn injury. Clin Med Res. 2006;4(4):250–5.PubMedCentralPubMed Barber RC, Chang LY, Arnoldo BD, Purdue GF, Hunt JL, Horton JW, et al. Innate immunity SNPs are associated with risk for severe sepsis after burn injury. Clin Med Res. 2006;4(4):250–5.PubMedCentralPubMed
3.
Zurück zum Zitat Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA. The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell. 1996;86(6):973–83.PubMed Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA. The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell. 1996;86(6):973–83.PubMed
4.
Zurück zum Zitat Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA. Pillars article: the dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell. 1996. 86: 973–983. J Immunol. 2012;188(11):5210–20.PubMed Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA. Pillars article: the dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell. 1996. 86: 973–983. J Immunol. 2012;188(11):5210–20.PubMed
6.
Zurück zum Zitat Medzhitov R, Preston-Hurlburt P, Janeway CA Jr. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature. 1997;388(6640):394–7. doi:10.1038/41131.PubMed Medzhitov R, Preston-Hurlburt P, Janeway CA Jr. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature. 1997;388(6640):394–7. doi:10.​1038/​41131.PubMed
11.
Zurück zum Zitat Takeuchi O, Hoshino K, Kawai T, Sanjo H, Takada H, Ogawa T, et al. Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components. Immunity. 1999;11(4):443–51.PubMed Takeuchi O, Hoshino K, Kawai T, Sanjo H, Takada H, Ogawa T, et al. Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components. Immunity. 1999;11(4):443–51.PubMed
12.
Zurück zum Zitat Takeuchi O, Sato S, Horiuchi T, Hoshino K, Takeda K, Dong Z, et al. Cutting edge: role of Toll-like receptor 1 in mediating immune response to microbial lipoproteins. J Immunol. 2002;169(1):10–4.PubMed Takeuchi O, Sato S, Horiuchi T, Hoshino K, Takeda K, Dong Z, et al. Cutting edge: role of Toll-like receptor 1 in mediating immune response to microbial lipoproteins. J Immunol. 2002;169(1):10–4.PubMed
13.
Zurück zum Zitat Takeuchi O, Kawai T, Muhlradt PF, Morr M, Radolf JD, Zychlinsky A, et al. Discrimination of bacterial lipoproteins by Toll-like receptor 6. Int Immunol. 2001;13(7):933–40.PubMed Takeuchi O, Kawai T, Muhlradt PF, Morr M, Radolf JD, Zychlinsky A, et al. Discrimination of bacterial lipoproteins by Toll-like receptor 6. Int Immunol. 2001;13(7):933–40.PubMed
14.
Zurück zum Zitat Netea MG, Van Der Graaf CA, Vonk AG, Verschueren I, Van Der Meer JW, Kullberg BJ. The role of Toll-like receptor (TLR) 2 and TLR4 in the host defense against disseminated candidiasis. J Infect Dis. 2002;185(10):1483–9. doi:10.1086/340511.PubMed Netea MG, Van Der Graaf CA, Vonk AG, Verschueren I, Van Der Meer JW, Kullberg BJ. The role of Toll-like receptor (TLR) 2 and TLR4 in the host defense against disseminated candidiasis. J Infect Dis. 2002;185(10):1483–9. doi:10.​1086/​340511.PubMed
16.
Zurück zum Zitat Alexopoulou L, Holt AC, Medzhitov R, Flavell RA. Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3. Nature. 2001;413(6857):732–8. doi:10.1038/35099560.PubMed Alexopoulou L, Holt AC, Medzhitov R, Flavell RA. Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3. Nature. 2001;413(6857):732–8. doi:10.​1038/​35099560.PubMed
17.
Zurück zum Zitat Ohashi K, Burkart V, Flohe S, Kolb H. Cutting edge: heat shock protein 60 is a putative endogenous ligand of the Toll-like receptor-4 complex. J Immunol. 2000;164(2):558–61.PubMed Ohashi K, Burkart V, Flohe S, Kolb H. Cutting edge: heat shock protein 60 is a putative endogenous ligand of the Toll-like receptor-4 complex. J Immunol. 2000;164(2):558–61.PubMed
18.
Zurück zum Zitat Roelofs MF, Boelens WC, Joosten LA, Abdollahi-Roodsaz S, Geurts J, Wunderink LU, et al. Identification of small heat shock protein B8 (HSP22) as a novel TLR4 ligand and potential involvement in the pathogenesis of rheumatoid arthritis. J Immunol. 2006;176(11):7021–7.PubMed Roelofs MF, Boelens WC, Joosten LA, Abdollahi-Roodsaz S, Geurts J, Wunderink LU, et al. Identification of small heat shock protein B8 (HSP22) as a novel TLR4 ligand and potential involvement in the pathogenesis of rheumatoid arthritis. J Immunol. 2006;176(11):7021–7.PubMed
19.
Zurück zum Zitat Hoshino K, Takeuchi O, Kawai T, Sanjo H, Ogawa T, Takeda Y, et al. Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product. J Immunol. 1999;162(7):3749–52.PubMed Hoshino K, Takeuchi O, Kawai T, Sanjo H, Ogawa T, Takeda Y, et al. Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product. J Immunol. 1999;162(7):3749–52.PubMed
20.
Zurück zum Zitat Nagai Y, Akashi S, Nagafuku M, Ogata M, Iwakura Y, Akira S, et al. Essential role of MD-2 in LPS responsiveness and TLR4 distribution. Nat Immunol. 2002;3(7):667–72. doi:10.1038/ni809.PubMed Nagai Y, Akashi S, Nagafuku M, Ogata M, Iwakura Y, Akira S, et al. Essential role of MD-2 in LPS responsiveness and TLR4 distribution. Nat Immunol. 2002;3(7):667–72. doi:10.​1038/​ni809.PubMed
21.
Zurück zum Zitat Jiang Z, Georgel P, Du X, Shamel L, Sovath S, Mudd S, et al. CD14 is required for MyD88-independent LPS signaling. Nat Immunol. 2005;6(6):565–70. doi:10.1038/ni1207.PubMed Jiang Z, Georgel P, Du X, Shamel L, Sovath S, Mudd S, et al. CD14 is required for MyD88-independent LPS signaling. Nat Immunol. 2005;6(6):565–70. doi:10.​1038/​ni1207.PubMed
22.
Zurück zum Zitat Jack RS, Fan X, Bernheiden M, Rune G, Ehlers M, Weber A, et al. Lipopolysaccharide-binding protein is required to combat a murine gram-negative bacterial infection. Nature. 1997;389(6652):742–5. doi:10.1038/39622.PubMed Jack RS, Fan X, Bernheiden M, Rune G, Ehlers M, Weber A, et al. Lipopolysaccharide-binding protein is required to combat a murine gram-negative bacterial infection. Nature. 1997;389(6652):742–5. doi:10.​1038/​39622.PubMed
23.
Zurück zum Zitat Hayashi F, Smith KD, Ozinsky A, Hawn TR, Yi EC, Goodlett DR, et al. The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature. 2001;410(6832):1099–103. doi:10.1038/35074106.PubMed Hayashi F, Smith KD, Ozinsky A, Hawn TR, Yi EC, Goodlett DR, et al. The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature. 2001;410(6832):1099–103. doi:10.​1038/​35074106.PubMed
24.
Zurück zum Zitat Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C, Akira S, et al. Species-specific recognition of single-stranded RNA via Toll-like receptor 7 and 8. Science. 2004;303(5663):1526–9. doi:10.1126/science.1093620.PubMed Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C, Akira S, et al. Species-specific recognition of single-stranded RNA via Toll-like receptor 7 and 8. Science. 2004;303(5663):1526–9. doi:10.​1126/​science.​1093620.PubMed
25.
Zurück zum Zitat Hemmi H, Kaisho T, Takeuchi O, Sato S, Sanjo H, Hoshino K, et al. Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat Immunol. 2002;3(2):196–200. doi:10.1038/ni758.PubMed Hemmi H, Kaisho T, Takeuchi O, Sato S, Sanjo H, Hoshino K, et al. Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat Immunol. 2002;3(2):196–200. doi:10.​1038/​ni758.PubMed
26.
Zurück zum Zitat Diebold SS, Kaisho T, Hemmi H, Akira S, Reis e Sousa C. Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science. 2004;303(5663):1529–31. doi:10.1126/science.1093616.PubMed Diebold SS, Kaisho T, Hemmi H, Akira S, Reis e Sousa C. Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science. 2004;303(5663):1529–31. doi:10.​1126/​science.​1093616.PubMed
28.
Zurück zum Zitat Hemmi H, Takeuchi O, Kawai T, Kaisho T, Sato S, Sanjo H, et al. A Toll-like receptor recognizes bacterial DNA. Nature. 2000;408(6813):740–5. doi:10.1038/35047123.PubMed Hemmi H, Takeuchi O, Kawai T, Kaisho T, Sato S, Sanjo H, et al. A Toll-like receptor recognizes bacterial DNA. Nature. 2000;408(6813):740–5. doi:10.​1038/​35047123.PubMed
30.
Zurück zum Zitat Zhang D, Zhang G, Hayden MS, Greenblatt MB, Bussey C, Flavell RA, et al. A Toll-like receptor that prevents infection by uropathogenic bacteria. Science. 2004;303(5663):1522–6. doi:10.1126/science.1094351.PubMed Zhang D, Zhang G, Hayden MS, Greenblatt MB, Bussey C, Flavell RA, et al. A Toll-like receptor that prevents infection by uropathogenic bacteria. Science. 2004;303(5663):1522–6. doi:10.​1126/​science.​1094351.PubMed
31.
Zurück zum Zitat Yarovinsky F, Zhang D, Andersen JF, Bannenberg GL, Serhan CN, Hayden MS, et al. TLR11 activation of dendritic cells by a protozoan profilin-like protein. Science. 2005;308(5728):1626–9. doi:10.1126/science.1109893.PubMed Yarovinsky F, Zhang D, Andersen JF, Bannenberg GL, Serhan CN, Hayden MS, et al. TLR11 activation of dendritic cells by a protozoan profilin-like protein. Science. 2005;308(5728):1626–9. doi:10.​1126/​science.​1109893.PubMed
34.
Zurück zum Zitat Janssens S, Burns K, Vercammen E, Tschopp J, Beyaert R. MyD88S, a splice variant of MyD88, differentially modulates NF-κB- and AP-1-dependent gene expression. FEBS Lett. 2003;548(1–3):103–7.PubMed Janssens S, Burns K, Vercammen E, Tschopp J, Beyaert R. MyD88S, a splice variant of MyD88, differentially modulates NF-κB- and AP-1-dependent gene expression. FEBS Lett. 2003;548(1–3):103–7.PubMed
36.
Zurück zum Zitat Lye E, Mirtsos C, Suzuki N, Suzuki S, Yeh WC. The role of interleukin 1 receptor-associated kinase-4 (IRAK-4) kinase activity in IRAK-4-mediated signaling. J Biol Chem. 2004;279(39):40653–8. doi:10.1074/jbc.M402666200.PubMed Lye E, Mirtsos C, Suzuki N, Suzuki S, Yeh WC. The role of interleukin 1 receptor-associated kinase-4 (IRAK-4) kinase activity in IRAK-4-mediated signaling. J Biol Chem. 2004;279(39):40653–8. doi:10.​1074/​jbc.​M402666200.PubMed
37.
Zurück zum Zitat Wang C, Deng L, Hong M, Akkaraju GR, Inoue J, Chen ZJ. TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature. 2001;412(6844):346–51. doi:10.1038/35085597.PubMed Wang C, Deng L, Hong M, Akkaraju GR, Inoue J, Chen ZJ. TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature. 2001;412(6844):346–51. doi:10.​1038/​35085597.PubMed
38.
Zurück zum Zitat Qian Y, Commane M, Ninomiya-Tsuji J, Matsumoto K, Li X. IRAK-mediated translocation of TRAF6 and TAB 2 in the interleukin-1-induced activation of NFκB. J Biol Chem. 2001;276(45):41661–7. doi:10.1074/jbc.M102262200.PubMed Qian Y, Commane M, Ninomiya-Tsuji J, Matsumoto K, Li X. IRAK-mediated translocation of TRAF6 and TAB 2 in the interleukin-1-induced activation of NFκB. J Biol Chem. 2001;276(45):41661–7. doi:10.​1074/​jbc.​M102262200.PubMed
39.
Zurück zum Zitat Jiang Z, Ninomiya-Tsuji J, Qian Y, Matsumoto K, Li X. Interleukin-1 (IL-1) receptor-associated kinase-dependent IL-1-induced signaling complexes phosphorylate TAK1 and TAB 2 at the plasma membrane and activate TAK1 in the cytosol. Mol Cell Biol. 2002;22(20):7158–67.PubMedCentralPubMed Jiang Z, Ninomiya-Tsuji J, Qian Y, Matsumoto K, Li X. Interleukin-1 (IL-1) receptor-associated kinase-dependent IL-1-induced signaling complexes phosphorylate TAK1 and TAB 2 at the plasma membrane and activate TAK1 in the cytosol. Mol Cell Biol. 2002;22(20):7158–67.PubMedCentralPubMed
41.
Zurück zum Zitat Mercurio F, Zhu H, Murray BW, Shevchenko A, Bennett BL, Li J, et al. IKK-1 and IKK-2: cytokine-activated IκB kinases essential for NF-κB activation. Science. 1997;278(5339):860–6.PubMed Mercurio F, Zhu H, Murray BW, Shevchenko A, Bennett BL, Li J, et al. IKK-1 and IKK-2: cytokine-activated IκB kinases essential for NF-κB activation. Science. 1997;278(5339):860–6.PubMed
42.
Zurück zum Zitat Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K, et al. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev. 2001;22(2):153–83.PubMed Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K, et al. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev. 2001;22(2):153–83.PubMed
43.
Zurück zum Zitat Buss H, Dorrie A, Schmitz ML, Hoffmann E, Resch K, Kracht M. Constitutive and interleukin-1-inducible phosphorylation of p65 NF-κB at serine 536 is mediated by multiple protein kinases including IκB kinase (IKK)-α, IKKβ, IKKε, TRAF family member-associated (TANK)-binding kinase 1 (TBK1), and an unknown kinase and couples p65 to TATA-binding protein-associated factor II31-mediated interleukin-8 transcription. J Biol Chem. 2004;279(53):55633–43. doi:10.1074/jbc.M409825200.PubMed Buss H, Dorrie A, Schmitz ML, Hoffmann E, Resch K, Kracht M. Constitutive and interleukin-1-inducible phosphorylation of p65 NF-κB at serine 536 is mediated by multiple protein kinases including IκB kinase (IKK)-α, IKKβ, IKKε, TRAF family member-associated (TANK)-binding kinase 1 (TBK1), and an unknown kinase and couples p65 to TATA-binding protein-associated factor II31-mediated interleukin-8 transcription. J Biol Chem. 2004;279(53):55633–43. doi:10.​1074/​jbc.​M409825200.PubMed
44.
Zurück zum Zitat Jefferies CA, Doyle S, Brunner C, Dunne A, Brint E, Wietek C, et al. Bruton’s tyrosine kinase is a Toll/interleukin-1 receptor domain-binding protein that participates in nuclear factor κB activation by Toll-like receptor 4. J Biol Chem. 2003;278(28):26258–64. doi:10.1074/jbc.M301484200.PubMed Jefferies CA, Doyle S, Brunner C, Dunne A, Brint E, Wietek C, et al. Bruton’s tyrosine kinase is a Toll/interleukin-1 receptor domain-binding protein that participates in nuclear factor κB activation by Toll-like receptor 4. J Biol Chem. 2003;278(28):26258–64. doi:10.​1074/​jbc.​M301484200.PubMed
45.
Zurück zum Zitat Doyle SL, Jefferies CA, O’Neill LA. Bruton’s tyrosine kinase is involved in p65-mediated transactivation and phosphorylation of p65 on serine 536 during NFκB activation by lipopolysaccharide. J Biol Chem. 2005;280(25):23496–501. doi:10.1074/jbc.C500053200.PubMed Doyle SL, Jefferies CA, O’Neill LA. Bruton’s tyrosine kinase is involved in p65-mediated transactivation and phosphorylation of p65 on serine 536 during NFκB activation by lipopolysaccharide. J Biol Chem. 2005;280(25):23496–501. doi:10.​1074/​jbc.​C500053200.PubMed
46.
Zurück zum Zitat Gray P, Dunne A, Brikos C, Jefferies CA, Doyle SL, O’Neill LA. MyD88 adapter-like (Mal) is phosphorylated by Bruton’s tyrosine kinase during TLR2 and TLR4 signal transduction. J Biol Chem. 2006;281(15):10489–95. doi:10.1074/jbc.M508892200.PubMed Gray P, Dunne A, Brikos C, Jefferies CA, Doyle SL, O’Neill LA. MyD88 adapter-like (Mal) is phosphorylated by Bruton’s tyrosine kinase during TLR2 and TLR4 signal transduction. J Biol Chem. 2006;281(15):10489–95. doi:10.​1074/​jbc.​M508892200.PubMed
48.
Zurück zum Zitat Jiang Z, Zamanian-Daryoush M, Nie H, Silva AM, Williams BR, Li X. Poly(I-C)-induced Toll-like receptor 3 (TLR3)-mediated activation of NFκB and MAP kinase is through an interleukin-1 receptor-associated kinase (IRAK)-independent pathway employing the signaling components TLR3–TRAF6–TAK1–TAB2–PKR. J Biol Chem. 2003;278(19):16713–9. doi:10.1074/jbc.M300562200.PubMed Jiang Z, Zamanian-Daryoush M, Nie H, Silva AM, Williams BR, Li X. Poly(I-C)-induced Toll-like receptor 3 (TLR3)-mediated activation of NFκB and MAP kinase is through an interleukin-1 receptor-associated kinase (IRAK)-independent pathway employing the signaling components TLR3–TRAF6–TAK1–TAB2–PKR. J Biol Chem. 2003;278(19):16713–9. doi:10.​1074/​jbc.​M300562200.PubMed
49.
50.
Zurück zum Zitat Meylan E, Burns K, Hofmann K, Blancheteau V, Martinon F, Kelliher M, et al. RIP1 is an essential mediator of Toll-like receptor 3-induced NF-κB activation. Nat Immunol. 2004;5(5):503–7. doi:10.1038/ni1061.PubMed Meylan E, Burns K, Hofmann K, Blancheteau V, Martinon F, Kelliher M, et al. RIP1 is an essential mediator of Toll-like receptor 3-induced NF-κB activation. Nat Immunol. 2004;5(5):503–7. doi:10.​1038/​ni1061.PubMed
51.
Zurück zum Zitat Sato S, Sugiyama M, Yamamoto M, Watanabe Y, Kawai T, Takeda K, et al. Toll/IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF) associates with TNF receptor-associated factor 6 and TANK-binding kinase 1, and activates two distinct transcription factors, NF-κB and IFN-regulatory factor-3, in the Toll-like receptor signaling. J Immunol. 2003;171(8):4304–10.PubMed Sato S, Sugiyama M, Yamamoto M, Watanabe Y, Kawai T, Takeda K, et al. Toll/IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF) associates with TNF receptor-associated factor 6 and TANK-binding kinase 1, and activates two distinct transcription factors, NF-κB and IFN-regulatory factor-3, in the Toll-like receptor signaling. J Immunol. 2003;171(8):4304–10.PubMed
52.
Zurück zum Zitat Altare F, Durandy A, Lammas D, Emile JF, Lamhamedi S, Le Deist F, et al. Impairment of mycobacterial immunity in human interleukin-12 receptor deficiency. Science. 1998;280(5368):1432–5.PubMed Altare F, Durandy A, Lammas D, Emile JF, Lamhamedi S, Le Deist F, et al. Impairment of mycobacterial immunity in human interleukin-12 receptor deficiency. Science. 1998;280(5368):1432–5.PubMed
56.
Zurück zum Zitat Molvig J, Baek L, Christensen P, Manogue KR, Vlassara H, Platz P, et al. Endotoxin-stimulated human monocyte secretion of interleukin 1, tumour necrosis factor alpha, and prostaglandin E2 shows stable interindividual differences. Scand J Immunol. 1988;27(6):705–16.PubMed Molvig J, Baek L, Christensen P, Manogue KR, Vlassara H, Platz P, et al. Endotoxin-stimulated human monocyte secretion of interleukin 1, tumour necrosis factor alpha, and prostaglandin E2 shows stable interindividual differences. Scand J Immunol. 1988;27(6):705–16.PubMed
57.
Zurück zum Zitat Westendorp RG, Langermans JA, Huizinga TW, Elouali AH, Verweij CL, Boomsma DI, et al. Genetic influence on cytokine production and fatal meningococcal disease. Lancet. 1997;349(9046):170–3.PubMed Westendorp RG, Langermans JA, Huizinga TW, Elouali AH, Verweij CL, Boomsma DI, et al. Genetic influence on cytokine production and fatal meningococcal disease. Lancet. 1997;349(9046):170–3.PubMed
58.
Zurück zum Zitat Wurfel MM, Park WY, Radella F, Ruzinski J, Sandstrom A, Strout J, et al. Identification of high and low responders to lipopolysaccharide in normal subjects: an unbiased approach to identify modulators of innate immunity. J Immunol. 2005;175(4):2570–8.PubMed Wurfel MM, Park WY, Radella F, Ruzinski J, Sandstrom A, Strout J, et al. Identification of high and low responders to lipopolysaccharide in normal subjects: an unbiased approach to identify modulators of innate immunity. J Immunol. 2005;175(4):2570–8.PubMed
59.
60.
Zurück zum Zitat Newport MJ, Huxley CM, Huston S, Hawrylowicz CM, Oostra BA, Williamson R, et al. A mutation in the interferon-gamma-receptor gene and susceptibility to mycobacterial infection. N Engl J Med. 1996;335(26):1941–9. doi:10.1056/NEJM199612263352602.PubMed Newport MJ, Huxley CM, Huston S, Hawrylowicz CM, Oostra BA, Williamson R, et al. A mutation in the interferon-gamma-receptor gene and susceptibility to mycobacterial infection. N Engl J Med. 1996;335(26):1941–9. doi:10.​1056/​NEJM199612263352​602.PubMed
62.
Zurück zum Zitat Puel A, Picard C, Ku CL, Smahi A, Casanova JL. Inherited disorders of NF-κB-mediated immunity in man. Curr Opin Immunol. 2004;16(1):34–41.PubMed Puel A, Picard C, Ku CL, Smahi A, Casanova JL. Inherited disorders of NF-κB-mediated immunity in man. Curr Opin Immunol. 2004;16(1):34–41.PubMed
66.
Zurück zum Zitat Lorenz E, Mira JP, Cornish KL, Arbour NC, Schwartz DA. A novel polymorphism in the Toll-like receptor 2 gene and its potential association with staphylococcal infection. Infect Immun. 2000;68(11):6398–401.PubMedCentralPubMed Lorenz E, Mira JP, Cornish KL, Arbour NC, Schwartz DA. A novel polymorphism in the Toll-like receptor 2 gene and its potential association with staphylococcal infection. Infect Immun. 2000;68(11):6398–401.PubMedCentralPubMed
67.
Zurück zum Zitat Schroder NW, Diterich I, Zinke A, Eckert J, Draing C, von Baehr V, et al. Heterozygous Arg753Gln polymorphism of human TLR-2 impairs immune activation by Borrelia burgdorferi and protects from late stage Lyme disease. J Immunol. 2005;175(4):2534–40.PubMed Schroder NW, Diterich I, Zinke A, Eckert J, Draing C, von Baehr V, et al. Heterozygous Arg753Gln polymorphism of human TLR-2 impairs immune activation by Borrelia burgdorferi and protects from late stage Lyme disease. J Immunol. 2005;175(4):2534–40.PubMed
70.
Zurück zum Zitat Kutukculer N, Yeniay BS, Aksu G, Berdeli A. Arg753Gln polymorphism of the human Toll-like receptor-2 gene in children with recurrent febrile infections. Biochem Genet. 2007;45(7–8):507–14. doi:10.1007/s10528-007-9091-0.PubMed Kutukculer N, Yeniay BS, Aksu G, Berdeli A. Arg753Gln polymorphism of the human Toll-like receptor-2 gene in children with recurrent febrile infections. Biochem Genet. 2007;45(7–8):507–14. doi:10.​1007/​s10528-007-9091-0.PubMed
71.
Zurück zum Zitat Schroder NW, Hermann C, Hamann L, Gobel UB, Hartung T, Schumann RR. High frequency of polymorphism Arg753Gln of the Toll-like receptor-2 gene detected by a novel allele-specific PCR. J Mol Med (Berl). 2003;81(6):368–72. doi:10.1007/s00109-003-0443-x. Schroder NW, Hermann C, Hamann L, Gobel UB, Hartung T, Schumann RR. High frequency of polymorphism Arg753Gln of the Toll-like receptor-2 gene detected by a novel allele-specific PCR. J Mol Med (Berl). 2003;81(6):368–72. doi:10.​1007/​s00109-003-0443-x.
72.
Zurück zum Zitat Ahmad-Nejad P, Denz C, Zimmer W, Wacker J, Bugert P, Weiss C, et al. The presence of functionally relevant Toll-like receptor polymorphisms does not significantly correlate with development or outcome of sepsis. Genet Test Mol Biomark. 2011;15(9):645–51. doi:10.1089/gtmb.2010.0258. Ahmad-Nejad P, Denz C, Zimmer W, Wacker J, Bugert P, Weiss C, et al. The presence of functionally relevant Toll-like receptor polymorphisms does not significantly correlate with development or outcome of sepsis. Genet Test Mol Biomark. 2011;15(9):645–51. doi:10.​1089/​gtmb.​2010.​0258.
73.
Zurück zum Zitat Lee SO, Brown RA, Kang SH, Abdel-Massih RC, Razonable RR. Toll-like receptor 2 polymorphism and Gram-positive bacterial infections after liver transplantation. Liver Transpl. 2011;17(9):1081–8. doi:10.1002/lt.22327.PubMed Lee SO, Brown RA, Kang SH, Abdel-Massih RC, Razonable RR. Toll-like receptor 2 polymorphism and Gram-positive bacterial infections after liver transplantation. Liver Transpl. 2011;17(9):1081–8. doi:10.​1002/​lt.​22327.PubMed
75.
Zurück zum Zitat Moura SB, Almeida LR, Guerra JB, Rocha GA, Camargos Rocha AM, Melo FF, et al. Toll-like receptor (TLR2, TLR4 and TLR5) gene polymorphisms and Helicobacter pylori infection in children with and without duodenal ulcer. Microbes Infect. 2008;10(14–15):1477–83. doi:10.1016/j.micinf.2008.08.009.PubMed Moura SB, Almeida LR, Guerra JB, Rocha GA, Camargos Rocha AM, Melo FF, et al. Toll-like receptor (TLR2, TLR4 and TLR5) gene polymorphisms and Helicobacter pylori infection in children with and without duodenal ulcer. Microbes Infect. 2008;10(14–15):1477–83. doi:10.​1016/​j.​micinf.​2008.​08.​009.PubMed
77.
Zurück zum Zitat Dalgic N, Tekin D, Kayaalti Z, Soylemezoglu T, Cakir E, Kilic B, et al. Arg753Gln polymorphism of the human Toll-like receptor 2 gene from infection to disease in pediatric tuberculosis. Hum Immunol. 2011;72(5):440–5. doi:10.1016/j.humimm.2011.02.001.PubMed Dalgic N, Tekin D, Kayaalti Z, Soylemezoglu T, Cakir E, Kilic B, et al. Arg753Gln polymorphism of the human Toll-like receptor 2 gene from infection to disease in pediatric tuberculosis. Hum Immunol. 2011;72(5):440–5. doi:10.​1016/​j.​humimm.​2011.​02.​001.PubMed
78.
Zurück zum Zitat Ogus AC, Yoldas B, Ozdemir T, Uguz A, Olcen S, Keser I, et al. The Arg753GLn polymorphism of the human Toll-like receptor 2 gene in tuberculosis disease. Eur Respir J. 2004;23(2):219–23.PubMed Ogus AC, Yoldas B, Ozdemir T, Uguz A, Olcen S, Keser I, et al. The Arg753GLn polymorphism of the human Toll-like receptor 2 gene in tuberculosis disease. Eur Respir J. 2004;23(2):219–23.PubMed
79.
Zurück zum Zitat Smirnova I, Mann N, Dols A, Derkx HH, Hibberd ML, Levin M, et al. Assay of locus-specific genetic load implicates rare Toll-like receptor 4 mutations in meningococcal susceptibility. Proc Natl Acad Sci USA. 2003;100(10):6075–80. doi:10.1073/pnas.1031605100.PubMedCentralPubMed Smirnova I, Mann N, Dols A, Derkx HH, Hibberd ML, Levin M, et al. Assay of locus-specific genetic load implicates rare Toll-like receptor 4 mutations in meningococcal susceptibility. Proc Natl Acad Sci USA. 2003;100(10):6075–80. doi:10.​1073/​pnas.​1031605100.PubMedCentralPubMed
80.
Zurück zum Zitat Pabst S, Yenice V, Lennarz M, Tuleta I, Nickenig G, Gillissen A, et al. Toll-like receptor 2 gene polymorphisms Arg677Trp and Arg753Gln in chronic obstructive pulmonary disease. Lung. 2009;187(3):173–8. doi:10.1007/s00408-009-9144-8.PubMed Pabst S, Yenice V, Lennarz M, Tuleta I, Nickenig G, Gillissen A, et al. Toll-like receptor 2 gene polymorphisms Arg677Trp and Arg753Gln in chronic obstructive pulmonary disease. Lung. 2009;187(3):173–8. doi:10.​1007/​s00408-009-9144-8.PubMed
81.
Zurück zum Zitat Yoon HJ, Choi JY, Kim CO, Park YS, Kim MS, Kim YK, et al. Lack of Toll-like receptor 4 and 2 polymorphisms in Korean patients with bacteremia. J Korean Med Sci. 2006;21(6):979–82.PubMedCentralPubMed Yoon HJ, Choi JY, Kim CO, Park YS, Kim MS, Kim YK, et al. Lack of Toll-like receptor 4 and 2 polymorphisms in Korean patients with bacteremia. J Korean Med Sci. 2006;21(6):979–82.PubMedCentralPubMed
82.
Zurück zum Zitat Everett B, Cameron B, Li H, Vollmer-Conna U, Davenport T, Hickie I, et al. Polymorphisms in Toll-like receptors-2 and -4 are not associated with disease manifestations in acute Q fever. Genes Immun. 2007;8(8):699–702. doi:10.1038/sj.gene.6364428.PubMed Everett B, Cameron B, Li H, Vollmer-Conna U, Davenport T, Hickie I, et al. Polymorphisms in Toll-like receptors-2 and -4 are not associated with disease manifestations in acute Q fever. Genes Immun. 2007;8(8):699–702. doi:10.​1038/​sj.​gene.​6364428.PubMed
84.
Zurück zum Zitat Kijpittayarit S, Eid AJ, Brown RA, Paya CV, Razonable RR. Relationship between Toll-like receptor 2 polymorphism and cytomegalovirus disease after liver transplantation. Clin Infect Dis. 2007;44(10):1315–20. doi:10.1086/514339.PubMed Kijpittayarit S, Eid AJ, Brown RA, Paya CV, Razonable RR. Relationship between Toll-like receptor 2 polymorphism and cytomegalovirus disease after liver transplantation. Clin Infect Dis. 2007;44(10):1315–20. doi:10.​1086/​514339.PubMed
85.
Zurück zum Zitat Kang SH, Abdel-Massih RC, Brown RA, Dierkhising RA, Kremers WK, Razonable RR. Homozygosity for the Toll-like receptor 2 R753Q single-nucleotide polymorphism is a risk factor for cytomegalovirus disease after liver transplantation. J Infect Dis. 2012;205(4):639–46. doi:10.1093/infdis/jir819.PubMedCentralPubMed Kang SH, Abdel-Massih RC, Brown RA, Dierkhising RA, Kremers WK, Razonable RR. Homozygosity for the Toll-like receptor 2 R753Q single-nucleotide polymorphism is a risk factor for cytomegalovirus disease after liver transplantation. J Infect Dis. 2012;205(4):639–46. doi:10.​1093/​infdis/​jir819.PubMedCentralPubMed
86.
Zurück zum Zitat Carvalho A, Cunha C, Carotti A, Aloisi T, Guarrera O, Di Ianni M, et al. Polymorphisms in Toll-like receptor genes and susceptibility to infections in allogeneic stem cell transplantation. Exp Hematol. 2009;37(9):1022–9. doi:10.1016/j.exphem.2009.06.004.PubMed Carvalho A, Cunha C, Carotti A, Aloisi T, Guarrera O, Di Ianni M, et al. Polymorphisms in Toll-like receptor genes and susceptibility to infections in allogeneic stem cell transplantation. Exp Hematol. 2009;37(9):1022–9. doi:10.​1016/​j.​exphem.​2009.​06.​004.PubMed
87.
Zurück zum Zitat Bochud PY, Magaret AS, Koelle DM, Aderem A, Wald A. Polymorphisms in TLR2 are associated with increased viral shedding and lesional rate in patients with genital herpes simplex virus type 2 infection. J Infect Dis. 2007;196(4):505–9. doi:10.1086/519693.PubMed Bochud PY, Magaret AS, Koelle DM, Aderem A, Wald A. Polymorphisms in TLR2 are associated with increased viral shedding and lesional rate in patients with genital herpes simplex virus type 2 infection. J Infect Dis. 2007;196(4):505–9. doi:10.​1086/​519693.PubMed
88.
Zurück zum Zitat Bochud PY, Hawn TR, Aderem A. Cutting edge: a Toll-like receptor 2 polymorphism that is associated with lepromatous leprosy is unable to mediate mycobacterial signaling. J Immunol. 2003;170(7):3451–4.PubMed Bochud PY, Hawn TR, Aderem A. Cutting edge: a Toll-like receptor 2 polymorphism that is associated with lepromatous leprosy is unable to mediate mycobacterial signaling. J Immunol. 2003;170(7):3451–4.PubMed
89.
Zurück zum Zitat Kang TJ, Lee SB, Chae GT. A polymorphism in the Toll-like receptor 2 is associated with IL-12 production from monocyte in lepromatous leprosy. Cytokine. 2002;20(2):56–62. doi:10.1006/cyto.2002.1982.PubMed Kang TJ, Lee SB, Chae GT. A polymorphism in the Toll-like receptor 2 is associated with IL-12 production from monocyte in lepromatous leprosy. Cytokine. 2002;20(2):56–62. doi:10.​1006/​cyto.​2002.​1982.PubMed
90.
Zurück zum Zitat Kang TJ, Chae GT. Detection of Toll-like receptor 2 (TLR2) mutation in the lepromatous leprosy patients. FEMS Immunol Med Microbiol. 2001;31(1):53–8.PubMed Kang TJ, Chae GT. Detection of Toll-like receptor 2 (TLR2) mutation in the lepromatous leprosy patients. FEMS Immunol Med Microbiol. 2001;31(1):53–8.PubMed
94.
Zurück zum Zitat Stappers MH, Thys Y, Oosting M, Plantinga TS, Ioana M, Reimnitz P, et al. TLR1, TLR2, and TLR6 gene polymorphisms are associated with increased susceptibility to complicated skin and skin structure infections. J Infect Dis. 2014;210(2):311–8. doi:10.1093/infdis/jiu080.PubMed Stappers MH, Thys Y, Oosting M, Plantinga TS, Ioana M, Reimnitz P, et al. TLR1, TLR2, and TLR6 gene polymorphisms are associated with increased susceptibility to complicated skin and skin structure infections. J Infect Dis. 2014;210(2):311–8. doi:10.​1093/​infdis/​jiu080.PubMed
95.
Zurück zum Zitat Bochud PY, Hawn TR, Siddiqui MR, Saunderson P, Britton S, Abraham I, et al. Toll-like receptor 2 (TLR2) polymorphisms are associated with reversal reaction in leprosy. J Infect Dis. 2008;197(2):253–61. doi:10.1086/524688.PubMedCentralPubMed Bochud PY, Hawn TR, Siddiqui MR, Saunderson P, Britton S, Abraham I, et al. Toll-like receptor 2 (TLR2) polymorphisms are associated with reversal reaction in leprosy. J Infect Dis. 2008;197(2):253–61. doi:10.​1086/​524688.PubMedCentralPubMed
96.
Zurück zum Zitat Thuong NT, Hawn TR, Thwaites GE, Chau TT, Lan NT, Quy HT, et al. A polymorphism in human TLR2 is associated with increased susceptibility to tuberculous meningitis. Genes Immun. 2007;8(5):422–8. doi:10.1038/sj.gene.6364405.PubMed Thuong NT, Hawn TR, Thwaites GE, Chau TT, Lan NT, Quy HT, et al. A polymorphism in human TLR2 is associated with increased susceptibility to tuberculous meningitis. Genes Immun. 2007;8(5):422–8. doi:10.​1038/​sj.​gene.​6364405.PubMed
97.
Zurück zum Zitat Pimentel-Nunes P, Teixeira AL, Pereira C, Gomes M, Brandao C, Rodrigues C, et al. Functional polymorphisms of Toll-like receptors 2 and 4 alter the risk for colorectal carcinoma in Europeans. Dig Liver Dis. 2012;. doi:10.1016/j.dld.2012.08.006.PubMed Pimentel-Nunes P, Teixeira AL, Pereira C, Gomes M, Brandao C, Rodrigues C, et al. Functional polymorphisms of Toll-like receptors 2 and 4 alter the risk for colorectal carcinoma in Europeans. Dig Liver Dis. 2012;. doi:10.​1016/​j.​dld.​2012.​08.​006.PubMed
98.
Zurück zum Zitat Yim JJ, Ding L, Schaffer AA, Park GY, Shim YS, Holland SM. A microsatellite polymorphism in intron 2 of human Toll-like receptor 2 gene: functional implications and racial differences. FEMS Immunol Med Microbiol. 2004;40(2):163–9. doi:10.1016/S0928-8244(03)00342-0.PubMed Yim JJ, Ding L, Schaffer AA, Park GY, Shim YS, Holland SM. A microsatellite polymorphism in intron 2 of human Toll-like receptor 2 gene: functional implications and racial differences. FEMS Immunol Med Microbiol. 2004;40(2):163–9. doi:10.​1016/​S0928-8244(03)00342-0.PubMed
99.
Zurück zum Zitat Yim JJ, Lee HW, Lee HS, Kim YW, Han SK, Shim YS, et al. The association between microsatellite polymorphisms in intron II of the human Toll-like receptor 2 gene and tuberculosis among Koreans. Genes Immun. 2006;7(2):150–5. doi:10.1038/sj.gene.6364274.PubMed Yim JJ, Lee HW, Lee HS, Kim YW, Han SK, Shim YS, et al. The association between microsatellite polymorphisms in intron II of the human Toll-like receptor 2 gene and tuberculosis among Koreans. Genes Immun. 2006;7(2):150–5. doi:10.​1038/​sj.​gene.​6364274.PubMed
100.
Zurück zum Zitat Motsinger-Reif AA, Antas PR, Oki NO, Levy S, Holland SM, Sterling TR. Polymorphisms in IL-1β, vitamin D receptor Fok1, and Toll-like receptor 2 are associated with extrapulmonary tuberculosis. BMC Med Genet. 2010;11:37. doi:10.1186/1471-2350-11-37.PubMedCentralPubMed Motsinger-Reif AA, Antas PR, Oki NO, Levy S, Holland SM, Sterling TR. Polymorphisms in IL-1β, vitamin D receptor Fok1, and Toll-like receptor 2 are associated with extrapulmonary tuberculosis. BMC Med Genet. 2010;11:37. doi:10.​1186/​1471-2350-11-37.PubMedCentralPubMed
101.
Zurück zum Zitat Yim JJ, Kim HJ, Kwon OJ, Koh WJ. Association between microsatellite polymorphisms in intron II of the human Toll-like receptor 2 gene and nontuberculous mycobacterial lung disease in a Korean population. Hum Immunol. 2008;69(9):572–6. doi:10.1016/j.humimm.2008.06.003.PubMed Yim JJ, Kim HJ, Kwon OJ, Koh WJ. Association between microsatellite polymorphisms in intron II of the human Toll-like receptor 2 gene and nontuberculous mycobacterial lung disease in a Korean population. Hum Immunol. 2008;69(9):572–6. doi:10.​1016/​j.​humimm.​2008.​06.​003.PubMed
103.
Zurück zum Zitat Velez DR, Wejse C, Stryjewski ME, Abbate E, Hulme WF, Myers JL, et al. Variants in Toll-like receptors 2 and 9 influence susceptibility to pulmonary tuberculosis in Caucasians, African–Americans, and West Africans. Hum Genet. 2010;127(1):65–73. doi:10.1007/s00439-009-0741-7.PubMedCentralPubMed Velez DR, Wejse C, Stryjewski ME, Abbate E, Hulme WF, Myers JL, et al. Variants in Toll-like receptors 2 and 9 influence susceptibility to pulmonary tuberculosis in Caucasians, African–Americans, and West Africans. Hum Genet. 2010;127(1):65–73. doi:10.​1007/​s00439-009-0741-7.PubMedCentralPubMed
104.
Zurück zum Zitat Berdeli A, Celik HA, Ozyurek R, Dogrusoz B, Aydin HH. TLR-2 gene Arg753Gln polymorphism is strongly associated with acute rheumatic fever in children. J Mol Med. 2005;83(7):535–41. doi:10.1007/s00109-005-0677-x.PubMed Berdeli A, Celik HA, Ozyurek R, Dogrusoz B, Aydin HH. TLR-2 gene Arg753Gln polymorphism is strongly associated with acute rheumatic fever in children. J Mol Med. 2005;83(7):535–41. doi:10.​1007/​s00109-005-0677-x.PubMed
105.
Zurück zum Zitat Duzgun N, Duman T, Haydardedeoglu FE, Tutkak H. The lack of genetic association of the Toll-like receptor 2 (TLR2) Arg753Gln and Arg677Trp polymorphisms with rheumatic heart disease. Clin Rheumatol. 2007;26(6):915–9. doi:10.1007/s10067-006-0432-x.PubMed Duzgun N, Duman T, Haydardedeoglu FE, Tutkak H. The lack of genetic association of the Toll-like receptor 2 (TLR2) Arg753Gln and Arg677Trp polymorphisms with rheumatic heart disease. Clin Rheumatol. 2007;26(6):915–9. doi:10.​1007/​s10067-006-0432-x.PubMed
107.
Zurück zum Zitat Emingil G, Berdeli A, Baylas H, Saygan BH, Gurkan A, Kose T, et al. Toll-like receptor 2 and 4 gene polymorphisms in generalized aggressive periodontitis. J Periodontol. 2007;78(10):1968–77. doi:10.1902/jop.2007.060360.PubMed Emingil G, Berdeli A, Baylas H, Saygan BH, Gurkan A, Kose T, et al. Toll-like receptor 2 and 4 gene polymorphisms in generalized aggressive periodontitis. J Periodontol. 2007;78(10):1968–77. doi:10.​1902/​jop.​2007.​060360.PubMed
108.
Zurück zum Zitat Zhu GX, Li CZ, Cao ZG, Corbet EF, Jin LJ. Toll-like receptors 2 and 4 gene polymorphisms in a Chinese population with periodontitis. Quintessence Int. 2008;39(3):217–26.PubMed Zhu GX, Li CZ, Cao ZG, Corbet EF, Jin LJ. Toll-like receptors 2 and 4 gene polymorphisms in a Chinese population with periodontitis. Quintessence Int. 2008;39(3):217–26.PubMed
109.
Zurück zum Zitat Berdeli A, Emingil G, Han Saygan B, Gurkan A, Atilla G, Kose T, et al. TLR2 Arg753Gly, TLR4 Asp299Gly and Thr399Ile gene polymorphisms are not associated with chronic periodontitis in a Turkish population. J Clin Periodontol. 2007;34(7):551–7. doi:10.1111/j.1600-051X.2007.01092.x.PubMed Berdeli A, Emingil G, Han Saygan B, Gurkan A, Atilla G, Kose T, et al. TLR2 Arg753Gly, TLR4 Asp299Gly and Thr399Ile gene polymorphisms are not associated with chronic periodontitis in a Turkish population. J Clin Periodontol. 2007;34(7):551–7. doi:10.​1111/​j.​1600-051X.​2007.​01092.​x.PubMed
110.
Zurück zum Zitat Imamura Y, Fujigaki Y, Oomori Y, Kuno T, Ota N, Wang PL. Polymorphism of genes encoding Toll-like receptors and inflammatory cytokines in periodontal disease in the Japanese population. J Int Acad Periodontol. 2008;10(3):95–102.PubMed Imamura Y, Fujigaki Y, Oomori Y, Kuno T, Ota N, Wang PL. Polymorphism of genes encoding Toll-like receptors and inflammatory cytokines in periodontal disease in the Japanese population. J Int Acad Periodontol. 2008;10(3):95–102.PubMed
111.
Zurück zum Zitat Krediet TG, Wiertsema SP, Vossers MJ, Hoeks SBEA, Fleer A, Ruven HJT, et al. Toll-like receptor 2 polymorphism is associated with preterm birth. Pediatr Res. 2007;62(4):474–6.PubMed Krediet TG, Wiertsema SP, Vossers MJ, Hoeks SBEA, Fleer A, Ruven HJT, et al. Toll-like receptor 2 polymorphism is associated with preterm birth. Pediatr Res. 2007;62(4):474–6.PubMed
112.
Zurück zum Zitat Pierik M, Joossens S, Van Steen K, Van Schuerbeek N, Vlietinck R, Rutgeerts P, et al. Toll-like receptor-1,-2, and-6 polymorphisms influence disease extension in inflammatory bowel diseases. Inflamm Bowel Dis. 2006;12(1):1–8. doi:10.1097/01.Mib.0000195389.11645.Ab.PubMed Pierik M, Joossens S, Van Steen K, Van Schuerbeek N, Vlietinck R, Rutgeerts P, et al. Toll-like receptor-1,-2, and-6 polymorphisms influence disease extension in inflammatory bowel diseases. Inflamm Bowel Dis. 2006;12(1):1–8. doi:10.​1097/​01.​Mib.​0000195389.​11645.​Ab.PubMed
113.
Zurück zum Zitat Hamann L, Gomma A, Schroder NWJ, Stamme C, Glaeser C, Schulz S, et al. A frequent Toll-like receptor (TLR)-2 polymorphism is a risk factor for coronary restenosis. J Mol Med. 2005;83(6):478–85. doi:10.1007/s00109-005-0643-7.PubMed Hamann L, Gomma A, Schroder NWJ, Stamme C, Glaeser C, Schulz S, et al. A frequent Toll-like receptor (TLR)-2 polymorphism is a risk factor for coronary restenosis. J Mol Med. 2005;83(6):478–85. doi:10.​1007/​s00109-005-0643-7.PubMed
114.
Zurück zum Zitat Guven M, Ismailoglu Z, Batar B, Unal S, Onaran I, Karadag B, et al. The effect of genetic polymorphisms of TLR2 and TLR4 in Turkish patients with coronary artery disease. Gene. 2015;558(1):99–102. doi:10.1016/j.gene.2014.12.047.PubMed Guven M, Ismailoglu Z, Batar B, Unal S, Onaran I, Karadag B, et al. The effect of genetic polymorphisms of TLR2 and TLR4 in Turkish patients with coronary artery disease. Gene. 2015;558(1):99–102. doi:10.​1016/​j.​gene.​2014.​12.​047.PubMed
115.
Zurück zum Zitat Ahmad-Nejad P, Mrabet-Dahbi S, Breuer K, Klotz M, Werfel T, Herz U, et al. The Toll-like receptor 2 R753Q polymorphism defines a subgroup of patients with atopic dermatitis having severe phenotype. J Allergy Clin Immunol. 2004;113(3):565–7. doi:10.1016/j.jaci.2003.12.583.PubMed Ahmad-Nejad P, Mrabet-Dahbi S, Breuer K, Klotz M, Werfel T, Herz U, et al. The Toll-like receptor 2 R753Q polymorphism defines a subgroup of patients with atopic dermatitis having severe phenotype. J Allergy Clin Immunol. 2004;113(3):565–7. doi:10.​1016/​j.​jaci.​2003.​12.​583.PubMed
116.
Zurück zum Zitat Mrabet-Dahbi S, Dalpke AH, Niebuhr M, Frey M, Draing C, Brand S, et al. The Toll-like receptor 2 R753Q mutation modifies cytokine production and Toll-like receptor expression in atopic dermatitis. J Allergy Clin Immunol. 2008;121(4):1013–9. doi:10.1016/j.jaci.2007.11.029.PubMed Mrabet-Dahbi S, Dalpke AH, Niebuhr M, Frey M, Draing C, Brand S, et al. The Toll-like receptor 2 R753Q mutation modifies cytokine production and Toll-like receptor expression in atopic dermatitis. J Allergy Clin Immunol. 2008;121(4):1013–9. doi:10.​1016/​j.​jaci.​2007.​11.​029.PubMed
117.
Zurück zum Zitat Niebuhr M, Langnickel J, Draing C, Renz H, Kapp A, Werfel T. Dysregulation of Toll-like receptor-2 (TLR-2)-induced effects in monocytes from patients with atopic dermatitis: impact of the TLR-2 R753Q polymorphism. Allergy. 2008;63(6):728–34. doi:10.1111/j.1398-9995.2008.01721.x.PubMed Niebuhr M, Langnickel J, Draing C, Renz H, Kapp A, Werfel T. Dysregulation of Toll-like receptor-2 (TLR-2)-induced effects in monocytes from patients with atopic dermatitis: impact of the TLR-2 R753Q polymorphism. Allergy. 2008;63(6):728–34. doi:10.​1111/​j.​1398-9995.​2008.​01721.​x.PubMed
118.
Zurück zum Zitat Jelavic TB, Barisic M, Hofman ID, Boraska V, Vrdoljak E, Peruzovic M, et al. Microsatelite GT polymorphism in the Toll-like receptor 2 is associated with colorectal cancer. Clin Genet. 2006;70(2):156–60. doi:10.1111/j.1399-0004.2006.00651.x. Jelavic TB, Barisic M, Hofman ID, Boraska V, Vrdoljak E, Peruzovic M, et al. Microsatelite GT polymorphism in the Toll-like receptor 2 is associated with colorectal cancer. Clin Genet. 2006;70(2):156–60. doi:10.​1111/​j.​1399-0004.​2006.​00651.​x.
120.
Zurück zum Zitat Bahrami H, Daneshmandi S, Heidarnazhad H, Pourfathollah AA. Lack of association between Toll like receptor-2 and Toll like receptor-4 gene polymorphisms and other feature in Iranian asthmatics patients. Iran J Allergy Asthma Immunol. 2015;14(1):48–54.PubMed Bahrami H, Daneshmandi S, Heidarnazhad H, Pourfathollah AA. Lack of association between Toll like receptor-2 and Toll like receptor-4 gene polymorphisms and other feature in Iranian asthmatics patients. Iran J Allergy Asthma Immunol. 2015;14(1):48–54.PubMed
121.
Zurück zum Zitat Redecke V, Hacker H, Datta SK, Fermin A, Pitha PM, Broide DH, et al. Cutting edge: activation of Toll-like receptor 2 induces a Th2 immune response and promotes experimental asthma. J Immunol. 2004;172(5):2739–43.PubMed Redecke V, Hacker H, Datta SK, Fermin A, Pitha PM, Broide DH, et al. Cutting edge: activation of Toll-like receptor 2 induces a Th2 immune response and promotes experimental asthma. J Immunol. 2004;172(5):2739–43.PubMed
122.
Zurück zum Zitat Yang IA, Barton SJ, Rorke S, Cakebread JA, Keith TP, Clough JB, et al. Toll-like receptor 4 polymorphism and severity of atopy in asthmatics. Genes Immun. 2004;5(1):41–5. doi:10.1038/sj.gene.6364037.PubMed Yang IA, Barton SJ, Rorke S, Cakebread JA, Keith TP, Clough JB, et al. Toll-like receptor 4 polymorphism and severity of atopy in asthmatics. Genes Immun. 2004;5(1):41–5. doi:10.​1038/​sj.​gene.​6364037.PubMed
123.
Zurück zum Zitat Eder W, Klimecki W, Yu LZ, von Mutius E, Riedler J, Braun-Fahrlander C, et al. Toll-like receptor 2 as a major gene for asthma in children of European farmers. J Allergy Clin Immunol. 2004;113(3):482–8. doi:10.1016/j.jaci.2003.12.374.PubMed Eder W, Klimecki W, Yu LZ, von Mutius E, Riedler J, Braun-Fahrlander C, et al. Toll-like receptor 2 as a major gene for asthma in children of European farmers. J Allergy Clin Immunol. 2004;113(3):482–8. doi:10.​1016/​j.​jaci.​2003.​12.​374.PubMed
124.
Zurück zum Zitat Nieters A, Beckmann L, Deeg E, Becker N. Gene polymorphisms in Toll-like receptors, interleukin-10, and interleukin-10 receptor alpha and lymphoma risk. Genes Immun. 2006;7(8):615–24. doi:10.1038/sj.gene.6364337.PubMed Nieters A, Beckmann L, Deeg E, Becker N. Gene polymorphisms in Toll-like receptors, interleukin-10, and interleukin-10 receptor alpha and lymphoma risk. Genes Immun. 2006;7(8):615–24. doi:10.​1038/​sj.​gene.​6364337.PubMed
125.
Zurück zum Zitat Sutherland AM, Walley KR, Russell JA. Polymorphisms in CD14, mannose-binding lectin, and Toll-like receptor-2 are associated with increased prevalence of infection in critically ill adults. Crit Care Med. 2005;33(3):638–44.PubMed Sutherland AM, Walley KR, Russell JA. Polymorphisms in CD14, mannose-binding lectin, and Toll-like receptor-2 are associated with increased prevalence of infection in critically ill adults. Crit Care Med. 2005;33(3):638–44.PubMed
126.
127.
Zurück zum Zitat Bjornvold M, Munthe-Kaas MC, Egeland T, Joner G, Dahl-Jorgensen K, Njolstad PR, et al. A TLR2 polymorphism is associated with type 1 diabetes and allergic asthma. Genes Immun. 2009;10(2):181–7. doi:10.1038/gene.2008.100.PubMed Bjornvold M, Munthe-Kaas MC, Egeland T, Joner G, Dahl-Jorgensen K, Njolstad PR, et al. A TLR2 polymorphism is associated with type 1 diabetes and allergic asthma. Genes Immun. 2009;10(2):181–7. doi:10.​1038/​gene.​2008.​100.PubMed
128.
Zurück zum Zitat Tomiyama R, Meguro A, Ota M, Katsuyama Y, Nishide T, Uemoto R, et al. Investigation of the association between Toll-like receptor 2 gene polymorphisms and Behcet’s disease in Japanese patients. Hu Immunol. 2009;70(1):41–4. doi:10.1016/j.humimm.2008.10.014. Tomiyama R, Meguro A, Ota M, Katsuyama Y, Nishide T, Uemoto R, et al. Investigation of the association between Toll-like receptor 2 gene polymorphisms and Behcet’s disease in Japanese patients. Hu Immunol. 2009;70(1):41–4. doi:10.​1016/​j.​humimm.​2008.​10.​014.
129.
Zurück zum Zitat Rahman HA, Khorshied MM, Khorshid OM, Mahgoub SM. Toll-like receptor 2 and 9 genetic polymorphisms and the susceptibility to B cell Non-Hodgkin Lymphoma in Egypt. Ann Hematol. 2014;93(11):1859–65. doi:10.1007/s00277-014-2131-z.PubMed Rahman HA, Khorshied MM, Khorshid OM, Mahgoub SM. Toll-like receptor 2 and 9 genetic polymorphisms and the susceptibility to B cell Non-Hodgkin Lymphoma in Egypt. Ann Hematol. 2014;93(11):1859–65. doi:10.​1007/​s00277-014-2131-z.PubMed
130.
131.
Zurück zum Zitat Takagi Y, Masamune A, Kume K, Satoh A, Kikuta K, Watanabe T, et al. Microsatellite polymorphism in intron 2 of human Toll-like receptor 2 gene is associated with susceptibility to acute pancreatitis in Japan. Hum Immunol. 2009;70(3):200–4. doi:10.1016/j.humimm.2009.01.006.PubMed Takagi Y, Masamune A, Kume K, Satoh A, Kikuta K, Watanabe T, et al. Microsatellite polymorphism in intron 2 of human Toll-like receptor 2 gene is associated with susceptibility to acute pancreatitis in Japan. Hum Immunol. 2009;70(3):200–4. doi:10.​1016/​j.​humimm.​2009.​01.​006.PubMed
133.
Zurück zum Zitat Theodoropoulos GE, Saridakis V, Karantanos T, Michalopoulos NV, Zagouri F, Kontogianni P, et al. Toll-like receptors gene polymorphisms may confer increased susceptibility to breast cancer development. Breast. 2012;21(4):534–8. doi:10.1016/j.breast.2012.04.001.PubMed Theodoropoulos GE, Saridakis V, Karantanos T, Michalopoulos NV, Zagouri F, Kontogianni P, et al. Toll-like receptors gene polymorphisms may confer increased susceptibility to breast cancer development. Breast. 2012;21(4):534–8. doi:10.​1016/​j.​breast.​2012.​04.​001.PubMed
135.
Zurück zum Zitat Singh V, Srivastava N, Kapoor R, Mittal RD. Single-nucleotide polymorphisms in Genes Encoding Toll-like Receptor -2, -3, -4, and -9 in a case–control study with bladder cancer susceptibility in a North Indian population. Arch Med Res. 2012;. doi:10.1016/j.arcmed.2012.10.008.PubMed Singh V, Srivastava N, Kapoor R, Mittal RD. Single-nucleotide polymorphisms in Genes Encoding Toll-like Receptor -2, -3, -4, and -9 in a case–control study with bladder cancer susceptibility in a North Indian population. Arch Med Res. 2012;. doi:10.​1016/​j.​arcmed.​2012.​10.​008.PubMed
136.
Zurück zum Zitat Pandey S, Mittal RD, Srivastava M, Srivastava K, Singh S, Srivastava S, et al. Impact of Toll-like receptors [TLR] 2 (-196 to -174 del) and TLR 4 (Asp299Gly, Thr399Ile) in cervical cancer susceptibility in North Indian women. Gynecol Oncol. 2009;114(3):501–5. doi:10.1016/j.ygyno.2009.05.032.PubMed Pandey S, Mittal RD, Srivastava M, Srivastava K, Singh S, Srivastava S, et al. Impact of Toll-like receptors [TLR] 2 (-196 to -174 del) and TLR 4 (Asp299Gly, Thr399Ile) in cervical cancer susceptibility in North Indian women. Gynecol Oncol. 2009;114(3):501–5. doi:10.​1016/​j.​ygyno.​2009.​05.​032.PubMed
137.
138.
Zurück zum Zitat Hishida A, Matsuo K, Goto Y, Naito M, Wakai K, Tajima K, et al. No associations of Toll-like receptor 2 (TLR2)-196 to-174del polymorphism with the risk of Helicobacter pylori seropositivity, gastric atrophy, and gastric cancer in Japanese. Gastric Cancer. 2010;13(4):251–7. doi:10.1007/s10120-010-0567-y.PubMed Hishida A, Matsuo K, Goto Y, Naito M, Wakai K, Tajima K, et al. No associations of Toll-like receptor 2 (TLR2)-196 to-174del polymorphism with the risk of Helicobacter pylori seropositivity, gastric atrophy, and gastric cancer in Japanese. Gastric Cancer. 2010;13(4):251–7. doi:10.​1007/​s10120-010-0567-y.PubMed
139.
140.
Zurück zum Zitat Omueti KO, Beyer JM, Johnson CM, Lyle EA, Tapping RI. Domain exchange between human Toll-like receptors 1 and 6 reveals a region required for lipopeptide discrimination. J Biol Chem. 2005;280(44):36616–25. doi:10.1074/jbc.M504320200.PubMed Omueti KO, Beyer JM, Johnson CM, Lyle EA, Tapping RI. Domain exchange between human Toll-like receptors 1 and 6 reveals a region required for lipopeptide discrimination. J Biol Chem. 2005;280(44):36616–25. doi:10.​1074/​jbc.​M504320200.PubMed
141.
Zurück zum Zitat Sun J, Wiklund F, Hsu FC, Balter K, Zheng SL, Johansson JE, et al. Interactions of sequence variants in interleukin-1 receptor-associated kinase4 and the Toll-like receptor 6-1-10 gene cluster increase prostate cancer risk. Cancer Epidemiol Biomark Prev. 2006;15(3):480–5. doi:10.1158/1055-9965.EPI-05-0645. Sun J, Wiklund F, Hsu FC, Balter K, Zheng SL, Johansson JE, et al. Interactions of sequence variants in interleukin-1 receptor-associated kinase4 and the Toll-like receptor 6-1-10 gene cluster increase prostate cancer risk. Cancer Epidemiol Biomark Prev. 2006;15(3):480–5. doi:10.​1158/​1055-9965.​EPI-05-0645.
142.
Zurück zum Zitat Omueti KO, Mazur DJ, Thompson KS, Lyle EA, Tapping RI. The polymorphism P315L of human Toll-like receptor 1 impairs innate immune sensing of microbial cell wall components. J Immunol. 2007;178(10):6387–94.PubMed Omueti KO, Mazur DJ, Thompson KS, Lyle EA, Tapping RI. The polymorphism P315L of human Toll-like receptor 1 impairs innate immune sensing of microbial cell wall components. J Immunol. 2007;178(10):6387–94.PubMed
143.
Zurück zum Zitat Kesh S, Mensah NY, Peterlongo P, Jaffe D, Hsu K, van den Brink M, et al. TLR1 and TLR6 polymorphisms are associated with susceptibility to invasive aspergillosis after allogeneic stem cell transplantation. Ann N Y Acad Sci. 2005;1062:95–103. doi:10.1196/annals.1358.012.PubMed Kesh S, Mensah NY, Peterlongo P, Jaffe D, Hsu K, van den Brink M, et al. TLR1 and TLR6 polymorphisms are associated with susceptibility to invasive aspergillosis after allogeneic stem cell transplantation. Ann N Y Acad Sci. 2005;1062:95–103. doi:10.​1196/​annals.​1358.​012.PubMed
144.
Zurück zum Zitat Verstraelen H, Verhelst R, Nuytinck L, Roelens K, De Meester E, De Vos D, et al. Gene polymorphisms of Toll-like and related recognition receptors in relation to the vaginal carriage of Gardnerella vaginalis and Atopobium vaginae. J Reprod Immunol. 2009;79(2):163–73. doi:10.1016/j.jri.2008.10.006.PubMed Verstraelen H, Verhelst R, Nuytinck L, Roelens K, De Meester E, De Vos D, et al. Gene polymorphisms of Toll-like and related recognition receptors in relation to the vaginal carriage of Gardnerella vaginalis and Atopobium vaginae. J Reprod Immunol. 2009;79(2):163–73. doi:10.​1016/​j.​jri.​2008.​10.​006.PubMed
145.
Zurück zum Zitat West TE, Chierakul W, Chantratita N, Limmathurotsakul D, Wuthiekanun V, Emond MJ, et al. Toll-like receptor 4 region genetic variants are associated with susceptibility to melioidosis. Genes Immun. 2012;13(1):38–46. doi:10.1038/gene.2011.49.PubMedCentralPubMed West TE, Chierakul W, Chantratita N, Limmathurotsakul D, Wuthiekanun V, Emond MJ, et al. Toll-like receptor 4 region genetic variants are associated with susceptibility to melioidosis. Genes Immun. 2012;13(1):38–46. doi:10.​1038/​gene.​2011.​49.PubMedCentralPubMed
146.
Zurück zum Zitat Hawn TR, Misch EA, Dunstan SJ, Thwaites GE, Lan NT, Quy HT, et al. A common human TLR1 polymorphism regulates the innate immune response to lipopeptides. Eur J Immunol. 2007;37(8):2280–9. doi:10.1002/eji.200737034.PubMed Hawn TR, Misch EA, Dunstan SJ, Thwaites GE, Lan NT, Quy HT, et al. A common human TLR1 polymorphism regulates the innate immune response to lipopeptides. Eur J Immunol. 2007;37(8):2280–9. doi:10.​1002/​eji.​200737034.PubMed
147.
Zurück zum Zitat Johnson CM, Lyle EA, Omueti KO, Stepensky VA, Yegin O, Alpsoy E, et al. Cutting edge: a common polymorphism impairs cell surface trafficking and functional responses of TLR1 but protects against leprosy. J Immunol. 2007;178(12):7520–4.PubMed Johnson CM, Lyle EA, Omueti KO, Stepensky VA, Yegin O, Alpsoy E, et al. Cutting edge: a common polymorphism impairs cell surface trafficking and functional responses of TLR1 but protects against leprosy. J Immunol. 2007;178(12):7520–4.PubMed
148.
Zurück zum Zitat Yang CA, Scheibenbogen C, Bauer S, Kleinle C, Wex T, Bornschein J, et al. A frequent Toll-like receptor 1 gene polymorphism affects NK- and T-cell IFN-γ production and is associated with Helicobacter pylori-induced gastric disease. Helicobacter. 2012;. doi:10.1111/hel.12001. Yang CA, Scheibenbogen C, Bauer S, Kleinle C, Wex T, Bornschein J, et al. A frequent Toll-like receptor 1 gene polymorphism affects NK- and T-cell IFN-γ production and is associated with Helicobacter pylori-induced gastric disease. Helicobacter. 2012;. doi:10.​1111/​hel.​12001.
149.
Zurück zum Zitat Alexopoulou L, Thomas V, Schnare M, Lobet Y, Anguita J, Schoen RT, et al. Hyporesponsiveness to vaccination with Borrelia burgdorferi OspA in humans and in TLR1- and TLR2-deficient mice. Nat Med. 2002;8(8):878–84. doi:10.1038/nm732.PubMed Alexopoulou L, Thomas V, Schnare M, Lobet Y, Anguita J, Schoen RT, et al. Hyporesponsiveness to vaccination with Borrelia burgdorferi OspA in humans and in TLR1- and TLR2-deficient mice. Nat Med. 2002;8(8):878–84. doi:10.​1038/​nm732.PubMed
150.
Zurück zum Zitat Leoratti FM, Farias L, Alves FP, Suarez-Mutis MC, Coura JR, Kalil J, et al. Variants in the Toll-like receptor signaling pathway and clinical outcomes of malaria. J Infect Dis. 2008;198(5):772–80. doi:10.1086/590440.PubMed Leoratti FM, Farias L, Alves FP, Suarez-Mutis MC, Coura JR, Kalil J, et al. Variants in the Toll-like receptor signaling pathway and clinical outcomes of malaria. J Infect Dis. 2008;198(5):772–80. doi:10.​1086/​590440.PubMed
152.
153.
Zurück zum Zitat Tantisira K, Klimecki WT, Lazarus R, Palmer LJ, Raby BA, Kwiatkowski DJ, et al. Toll-like receptor 6 gene (TLR6): single-nucleotide polymorphism frequencies and preliminary association with the diagnosis of asthma. Genes Immun. 2004;5(5):343–6. doi:10.1038/sj.gene.6364096.PubMed Tantisira K, Klimecki WT, Lazarus R, Palmer LJ, Raby BA, Kwiatkowski DJ, et al. Toll-like receptor 6 gene (TLR6): single-nucleotide polymorphism frequencies and preliminary association with the diagnosis of asthma. Genes Immun. 2004;5(5):343–6. doi:10.​1038/​sj.​gene.​6364096.PubMed
155.
Zurück zum Zitat Sun J, Wiklund F, Zheng SL, Chang B, Balter K, Li L, et al. Sequence variants in Toll-like receptor gene cluster (TLR6-TLR1-TLR10) and prostate cancer risk. J Natl Cancer Inst. 2005;97(7):525–32. doi:10.1093/jnci/dji070.PubMed Sun J, Wiklund F, Zheng SL, Chang B, Balter K, Li L, et al. Sequence variants in Toll-like receptor gene cluster (TLR6-TLR1-TLR10) and prostate cancer risk. J Natl Cancer Inst. 2005;97(7):525–32. doi:10.​1093/​jnci/​dji070.PubMed
156.
Zurück zum Zitat Stevens VL, Hsing AW, Talbot JT, Zheng SL, Sun J, Chen J, et al. Genetic variation in the Toll-like receptor gene cluster (TLR10–TLR1–TLR6) and prostate cancer risk. Int J Cancer. 2008;123(11):2644–50. doi:10.1002/ijc.23826.PubMed Stevens VL, Hsing AW, Talbot JT, Zheng SL, Sun J, Chen J, et al. Genetic variation in the Toll-like receptor gene cluster (TLR10–TLR1–TLR6) and prostate cancer risk. Int J Cancer. 2008;123(11):2644–50. doi:10.​1002/​ijc.​23826.PubMed
157.
Zurück zum Zitat Chen YC, Giovannucci E, Kraft P, Lazarus R, Hunter DJ. Association between Toll-like receptor gene cluster (TLR6, TLR1, and TLR10) and prostate cancer. Cancer Epidemiol Biomark Prev. 2007;16(10):1982–9. doi:10.1158/1055-9965.Epi-07-0325. Chen YC, Giovannucci E, Kraft P, Lazarus R, Hunter DJ. Association between Toll-like receptor gene cluster (TLR6, TLR1, and TLR10) and prostate cancer. Cancer Epidemiol Biomark Prev. 2007;16(10):1982–9. doi:10.​1158/​1055-9965.​Epi-07-0325.
158.
Zurück zum Zitat Schippers EF, van ‘t Veer C, van Voorden S, Martina CA, Huizinga TW, le Cessie S, et al. IL-10 and Toll-like receptor-4 polymorphisms and the in vivo and ex vivo response to endotoxin. Cytokine. 2005;29(5):215–28. doi:10.1016/j.cyto.2004.12.005.PubMed Schippers EF, van ‘t Veer C, van Voorden S, Martina CA, Huizinga TW, le Cessie S, et al. IL-10 and Toll-like receptor-4 polymorphisms and the in vivo and ex vivo response to endotoxin. Cytokine. 2005;29(5):215–28. doi:10.​1016/​j.​cyto.​2004.​12.​005.PubMed
160.
Zurück zum Zitat van der Graaf C, Kullberg BJ, Joosten L, Verver-Jansen T, Jacobs L, Van der Meer JW, et al. Functional consequences of the Asp299Gly Toll-like receptor-4 polymorphism. Cytokine. 2005;30(5):264–8. doi:10.1016/j.cyto.2005.02.001.PubMed van der Graaf C, Kullberg BJ, Joosten L, Verver-Jansen T, Jacobs L, Van der Meer JW, et al. Functional consequences of the Asp299Gly Toll-like receptor-4 polymorphism. Cytokine. 2005;30(5):264–8. doi:10.​1016/​j.​cyto.​2005.​02.​001.PubMed
161.
Zurück zum Zitat Rallabhandi P, Bell J, Boukhvalova MS, Medvedev A, Lorenz E, Arditi M, et al. Analysis of TLR4 polymorphic variants: new insights into TLR4/MD-2/CD14 stoichiometry, structure, and signaling. J Immunol. 2006;177(1):322–32.PubMed Rallabhandi P, Bell J, Boukhvalova MS, Medvedev A, Lorenz E, Arditi M, et al. Analysis of TLR4 polymorphic variants: new insights into TLR4/MD-2/CD14 stoichiometry, structure, and signaling. J Immunol. 2006;177(1):322–32.PubMed
162.
Zurück zum Zitat Child NJ, Yang IA, Pulletz MC, de Courcy-Golder K, Andrews AL, Pappachan VJ, et al. Polymorphisms in Toll-like receptor 4 and the systemic inflammatory response syndrome. Biochem Soc Trans. 2003;31(Pt 3):652–3. doi:10.1042/BST0310652.PubMed Child NJ, Yang IA, Pulletz MC, de Courcy-Golder K, Andrews AL, Pappachan VJ, et al. Polymorphisms in Toll-like receptor 4 and the systemic inflammatory response syndrome. Biochem Soc Trans. 2003;31(Pt 3):652–3. doi:10.​1042/​BST0310652.PubMed
163.
Zurück zum Zitat Lorenz E, Mira JP, Frees KL, Schwartz DA. Relevance of mutations in the TLR4 receptor in patients with gram-negative septic shock. Arch Intern Med. 2002;162(9):1028–32.PubMed Lorenz E, Mira JP, Frees KL, Schwartz DA. Relevance of mutations in the TLR4 receptor in patients with gram-negative septic shock. Arch Intern Med. 2002;162(9):1028–32.PubMed
164.
Zurück zum Zitat Agnese DM, Calvano JE, Hahm SJ, Coyle SM, Corbett SA, Calvano SE, et al. Human Toll-like receptor 4 mutations but not CD14 polymorphisms are associated with an increased risk of gram-negative infections. J Infect Dis. 2002;186(10):1522–5. doi:10.1086/344893.PubMed Agnese DM, Calvano JE, Hahm SJ, Coyle SM, Corbett SA, Calvano SE, et al. Human Toll-like receptor 4 mutations but not CD14 polymorphisms are associated with an increased risk of gram-negative infections. J Infect Dis. 2002;186(10):1522–5. doi:10.​1086/​344893.PubMed
165.
Zurück zum Zitat Carregaro F, Carta A, Cordeiro JA, Lobo SM, Silva EH, Leopoldino AM. Polymorphisms IL10-819 and TLR-2 are potentially associated with sepsis in Brazilian patients. Mem Inst Oswaldo Cruz. 2010;105(5):649–56.PubMed Carregaro F, Carta A, Cordeiro JA, Lobo SM, Silva EH, Leopoldino AM. Polymorphisms IL10-819 and TLR-2 are potentially associated with sepsis in Brazilian patients. Mem Inst Oswaldo Cruz. 2010;105(5):649–56.PubMed
166.
Zurück zum Zitat Feterowski C, Emmanuilidis K, Miethke T, Gerauer K, Rump M, Ulm K, et al. Effects of functional Toll-like receptor-4 mutations on the immune response to human and experimental sepsis. Immunology. 2003;109(3):426–31.PubMedCentralPubMed Feterowski C, Emmanuilidis K, Miethke T, Gerauer K, Rump M, Ulm K, et al. Effects of functional Toll-like receptor-4 mutations on the immune response to human and experimental sepsis. Immunology. 2003;109(3):426–31.PubMedCentralPubMed
167.
Zurück zum Zitat Faber J, Meyer CU, Gemmer C, Russo A, Finn A, Murdoch C, et al. Human Toll-like receptor 4 mutations are associated with susceptibility to invasive meningococcal disease in infancy. Pediatr Infect Dis J. 2006;25(1):80–1.PubMed Faber J, Meyer CU, Gemmer C, Russo A, Finn A, Murdoch C, et al. Human Toll-like receptor 4 mutations are associated with susceptibility to invasive meningococcal disease in infancy. Pediatr Infect Dis J. 2006;25(1):80–1.PubMed
168.
Zurück zum Zitat Read RC, Pullin J, Gregory S, Borrow R, Kaczmarski EB, di Giovine FS, et al. A functional polymorphism of Toll-like receptor 4 is not associated with likelihood or severity of meningococcal disease. J Infect Dis. 2001;184(5):640–2. doi:10.1086/322798.PubMed Read RC, Pullin J, Gregory S, Borrow R, Kaczmarski EB, di Giovine FS, et al. A functional polymorphism of Toll-like receptor 4 is not associated with likelihood or severity of meningococcal disease. J Infect Dis. 2001;184(5):640–2. doi:10.​1086/​322798.PubMed
169.
Zurück zum Zitat Allen A, Obaro S, Bojang K, Awomoyi AA, Greenwood BM, Whittle H, et al. Variation in Toll-like receptor 4 and susceptibility to group A meningococcal meningitis in Gambian children. Pediatr Infect Dis J. 2003;22(11):1018–9.PubMed Allen A, Obaro S, Bojang K, Awomoyi AA, Greenwood BM, Whittle H, et al. Variation in Toll-like receptor 4 and susceptibility to group A meningococcal meningitis in Gambian children. Pediatr Infect Dis J. 2003;22(11):1018–9.PubMed
171.
Zurück zum Zitat Tian T, Jin S, Dong J, Li G. Lack of association between Toll-like receptor 4 gene Asp299Gly and Thr399Ile polymorphisms and tuberculosis susceptibility: a meta-analysis. Infect Genet Evol. 2013;14:156–60. doi:10.1016/j.meegid.2012.11.009.PubMed Tian T, Jin S, Dong J, Li G. Lack of association between Toll-like receptor 4 gene Asp299Gly and Thr399Ile polymorphisms and tuberculosis susceptibility: a meta-analysis. Infect Genet Evol. 2013;14:156–60. doi:10.​1016/​j.​meegid.​2012.​11.​009.PubMed
173.
Zurück zum Zitat Bochud PY, Sinsimer D, Aderem A, Siddiqui MR, Saunderson P, Britton S, et al. Polymorphisms in Toll-like receptor 4 (TLR4) are associated with protection against leprosy. Eur J Clin Microbiol Infect Dis. 2009;28(9):1055–65. doi:10.1007/s10096-009-0746-0.PubMedCentralPubMed Bochud PY, Sinsimer D, Aderem A, Siddiqui MR, Saunderson P, Britton S, et al. Polymorphisms in Toll-like receptor 4 (TLR4) are associated with protection against leprosy. Eur J Clin Microbiol Infect Dis. 2009;28(9):1055–65. doi:10.​1007/​s10096-009-0746-0.PubMedCentralPubMed
174.
Zurück zum Zitat Yuan FF, Marks K, Wong M, Watson S, de Leon E, McIntyre PB, et al. Clinical relevance of TLR2, TLR4, CD14 and FcgammaRIIA gene polymorphisms in Streptococcus pneumoniae infection. Immunol Cell Biol. 2008;86(3):268–70. doi:10.1038/sj.icb.7100155.PubMed Yuan FF, Marks K, Wong M, Watson S, de Leon E, McIntyre PB, et al. Clinical relevance of TLR2, TLR4, CD14 and FcgammaRIIA gene polymorphisms in Streptococcus pneumoniae infection. Immunol Cell Biol. 2008;86(3):268–70. doi:10.​1038/​sj.​icb.​7100155.PubMed
175.
Zurück zum Zitat Karoly E, Fekete A, Banki NF, Szebeni B, Vannay A, Szabo AJ, et al. Heat shock protein 72 (HSPA1B) gene polymorphism and Toll-like receptor (TLR) 4 mutation are associated with increased risk of urinary tract infection in children. Pediatr Res. 2007;61(3):371–4. doi:10.1203/pdr.0b013e318030d1f4.PubMed Karoly E, Fekete A, Banki NF, Szebeni B, Vannay A, Szabo AJ, et al. Heat shock protein 72 (HSPA1B) gene polymorphism and Toll-like receptor (TLR) 4 mutation are associated with increased risk of urinary tract infection in children. Pediatr Res. 2007;61(3):371–4. doi:10.​1203/​pdr.​0b013e318030d1f4​.PubMed
177.
Zurück zum Zitat Ertan P, Berdeli A, Yilmaz O, Gonulal DA, Yuksel H. LY96, UPKIB mutations and TLR4, CD14, MBL polymorphisms in children with urinary tract infection. Indian J Pediatr. 2011;78(10):1229–33. doi:10.1007/s12098-011-0399-8.PubMed Ertan P, Berdeli A, Yilmaz O, Gonulal DA, Yuksel H. LY96, UPKIB mutations and TLR4, CD14, MBL polymorphisms in children with urinary tract infection. Indian J Pediatr. 2011;78(10):1229–33. doi:10.​1007/​s12098-011-0399-8.PubMed
181.
Zurück zum Zitat Kurt-Jones EA, Popova L, Kwinn L, Haynes LM, Jones LP, Tripp RA, et al. Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus. Nat Immunol. 2000;1(5):398–401. doi:10.1038/80833.PubMed Kurt-Jones EA, Popova L, Kwinn L, Haynes LM, Jones LP, Tripp RA, et al. Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus. Nat Immunol. 2000;1(5):398–401. doi:10.​1038/​80833.PubMed
182.
Zurück zum Zitat Tal G, Mandelberg A, Dalal I, Cesar K, Somekh E, Tal A, et al. Association between common Toll-like receptor 4 mutations and severe respiratory syncytial virus disease. J Infect Dis. 2004;189(11):2057–63. doi:10.1086/420830.PubMed Tal G, Mandelberg A, Dalal I, Cesar K, Somekh E, Tal A, et al. Association between common Toll-like receptor 4 mutations and severe respiratory syncytial virus disease. J Infect Dis. 2004;189(11):2057–63. doi:10.​1086/​420830.PubMed
183.
184.
Zurück zum Zitat Awomoyi AA, Rallabhandi P, Pollin TI, Lorenz E, Sztein MB, Boukhvalova MS, et al. Association of TLR4 polymorphisms with symptomatic respiratory syncytial virus infection in high-risk infants and young children. J Immunol. 2007;179(5):3171–7.PubMed Awomoyi AA, Rallabhandi P, Pollin TI, Lorenz E, Sztein MB, Boukhvalova MS, et al. Association of TLR4 polymorphisms with symptomatic respiratory syncytial virus infection in high-risk infants and young children. J Immunol. 2007;179(5):3171–7.PubMed
185.
Zurück zum Zitat Paulus SC, Hirschfeld AF, Victor RE, Brunstein J, Thomas E, Turvey SE. Common human Toll-like receptor 4 polymorphisms-role in susceptibility to respiratory syncytial virus infection and functional immunological relevance. Clin Immunol. 2007;123(3):252–7. doi:10.1016/j.clim.2007.03.003.PubMed Paulus SC, Hirschfeld AF, Victor RE, Brunstein J, Thomas E, Turvey SE. Common human Toll-like receptor 4 polymorphisms-role in susceptibility to respiratory syncytial virus infection and functional immunological relevance. Clin Immunol. 2007;123(3):252–7. doi:10.​1016/​j.​clim.​2007.​03.​003.PubMed
186.
Zurück zum Zitat Lofgren J, Marttila R, Renko M, Ramet M, Hallman M. Toll-like receptor 4 Asp299Gly polymorphism in respiratory syncytial virus epidemics. Pediatr Pulmonol. 2010;45(7):687–92. doi:10.1002/ppul.21248.PubMed Lofgren J, Marttila R, Renko M, Ramet M, Hallman M. Toll-like receptor 4 Asp299Gly polymorphism in respiratory syncytial virus epidemics. Pediatr Pulmonol. 2010;45(7):687–92. doi:10.​1002/​ppul.​21248.PubMed
187.
Zurück zum Zitat Goutaki M, Haidopoulou K, Pappa S, Tsakiridis P, Frydas E, Eboriadou M, et al. The role of TLR4 and CD14 polymorphisms in the pathogenesis of respiratory syncytial virus bronchiolitis in greek infants. Int J Immunopathol Pharmacol. 2014;27(4):563–72.PubMed Goutaki M, Haidopoulou K, Pappa S, Tsakiridis P, Frydas E, Eboriadou M, et al. The role of TLR4 and CD14 polymorphisms in the pathogenesis of respiratory syncytial virus bronchiolitis in greek infants. Int J Immunopathol Pharmacol. 2014;27(4):563–72.PubMed
188.
Zurück zum Zitat Bhuvanendran S, Hussin HM, Meran LP, Anthony AA, Zhang L, Burch LH, et al. Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms and typhoid susceptibility in Asian Malay population in Malaysia. Microbes Infect. 2011;13(10):844–51. doi:10.1016/j.micinf.2011.04.007.PubMed Bhuvanendran S, Hussin HM, Meran LP, Anthony AA, Zhang L, Burch LH, et al. Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms and typhoid susceptibility in Asian Malay population in Malaysia. Microbes Infect. 2011;13(10):844–51. doi:10.​1016/​j.​micinf.​2011.​04.​007.PubMed
189.
Zurück zum Zitat Van der Graaf CA, Netea MG, Morre SA, Den Heijer M, Verweij PE, Van der Meer JW, et al. Toll-like receptor 4 Asp299Gly/Thr399Ile polymorphisms are a risk factor for Candida bloodstream infection. Eur Cytokine Netw. 2006;17(1):29–34.PubMed Van der Graaf CA, Netea MG, Morre SA, Den Heijer M, Verweij PE, Van der Meer JW, et al. Toll-like receptor 4 Asp299Gly/Thr399Ile polymorphisms are a risk factor for Candida bloodstream infection. Eur Cytokine Netw. 2006;17(1):29–34.PubMed
191.
Zurück zum Zitat Mockenhaupt FP, Cramer JP, Hamann L, Stegemann MS, Eckert J, Oh NR, et al. Toll-like receptor (TLR) polymorphisms in African children: common TLR-4 variants predispose to severe malaria. Proc Natl Acad Sci USA. 2006;103(1):177–82. doi:10.1073/pnas.0506803102.PubMedCentralPubMed Mockenhaupt FP, Cramer JP, Hamann L, Stegemann MS, Eckert J, Oh NR, et al. Toll-like receptor (TLR) polymorphisms in African children: common TLR-4 variants predispose to severe malaria. Proc Natl Acad Sci USA. 2006;103(1):177–82. doi:10.​1073/​pnas.​0506803102.PubMedCentralPubMed
192.
Zurück zum Zitat Mockenhaupt FP, Hamann L, von Gaertner C, Bedu-Addo G, von Kleinsorgen C, Schumann RR, et al. Common polymorphisms of Toll-like receptors 4 and 9 are associated with the clinical manifestation of malaria during pregnancy. J Infect Dis. 2006;194(2):184–8. doi:10.1086/505152.PubMed Mockenhaupt FP, Hamann L, von Gaertner C, Bedu-Addo G, von Kleinsorgen C, Schumann RR, et al. Common polymorphisms of Toll-like receptors 4 and 9 are associated with the clinical manifestation of malaria during pregnancy. J Infect Dis. 2006;194(2):184–8. doi:10.​1086/​505152.PubMed
193.
Zurück zum Zitat Kuong VV, Avetikov DS, Shlykova OA, Izmailova OV, Kaidashev IP. Incidence of odontogenic phlegmon associated with polymorphic variant 896A/G of gene TLR4, but not with 2258G/A of gene TLR2. Klin Khir. 2014;10:54–6.PubMed Kuong VV, Avetikov DS, Shlykova OA, Izmailova OV, Kaidashev IP. Incidence of odontogenic phlegmon associated with polymorphic variant 896A/G of gene TLR4, but not with 2258G/A of gene TLR2. Klin Khir. 2014;10:54–6.PubMed
194.
Zurück zum Zitat Al-Qahtani AA, Al-Anazi MR, Al-Zoghaibi F, Abdo AA, Sanai FM, Khan MQ, et al. The association of Toll-like receptor 4 polymorphism with hepatitis C virus infection in Saudi Arabian patients. Biomed Res Int. 2014;2014:357062. doi:10.1155/2014/357062.PubMedCentralPubMed Al-Qahtani AA, Al-Anazi MR, Al-Zoghaibi F, Abdo AA, Sanai FM, Khan MQ, et al. The association of Toll-like receptor 4 polymorphism with hepatitis C virus infection in Saudi Arabian patients. Biomed Res Int. 2014;2014:357062. doi:10.​1155/​2014/​357062.PubMedCentralPubMed
197.
Zurück zum Zitat Morre SA, Murillo LS, Spaargaren J, Fennema HS, Pena AS. Role of the Toll-like receptor 4 Asp299Gly polymorphism in susceptibility to Candida albicans infection. J Infect Dis. 2002;186(9):1377–9. doi:10.1086/344328 (author reply 9).PubMed Morre SA, Murillo LS, Spaargaren J, Fennema HS, Pena AS. Role of the Toll-like receptor 4 Asp299Gly polymorphism in susceptibility to Candida albicans infection. J Infect Dis. 2002;186(9):1377–9. doi:10.​1086/​344328 (author reply 9).PubMed
198.
Zurück zum Zitat Rasouli M, Keshavarz M, Kalani M, Moravej A, Kiany S, Badiee P. Toll-like receptor 4 (TLR4) polymorphisms in Iranian patients with visceral leishmaniasis. Mol Biol Rep. 2012;39(12):10795–802. doi:10.1007/s11033-012-1973-5.PubMed Rasouli M, Keshavarz M, Kalani M, Moravej A, Kiany S, Badiee P. Toll-like receptor 4 (TLR4) polymorphisms in Iranian patients with visceral leishmaniasis. Mol Biol Rep. 2012;39(12):10795–802. doi:10.​1007/​s11033-012-1973-5.PubMed
200.
Zurück zum Zitat Zafra G, Florez O, Morillo CA, Echeverria LE, Martin J, Gonzalez CI. Polymorphisms of Toll-like receptor 2 and 4 genes in Chagas disease. Mem Inst Oswaldo Cruz. 2008;103(1):27–30.PubMed Zafra G, Florez O, Morillo CA, Echeverria LE, Martin J, Gonzalez CI. Polymorphisms of Toll-like receptor 2 and 4 genes in Chagas disease. Mem Inst Oswaldo Cruz. 2008;103(1):27–30.PubMed
203.
Zurück zum Zitat Davis ML, LeVan TD, Yu F, Sayles H, Sokolove J, Robinson W, et al. Associations of Toll-like receptor (TLR)-4 single nucleotide polymorphisms and rheumatoid arthritis disease progression: an observational cohort study. Int Immunopharmacol. 2015;24(2):346–52. doi:10.1016/j.intimp.2014.12.030.PubMed Davis ML, LeVan TD, Yu F, Sayles H, Sokolove J, Robinson W, et al. Associations of Toll-like receptor (TLR)-4 single nucleotide polymorphisms and rheumatoid arthritis disease progression: an observational cohort study. Int Immunopharmacol. 2015;24(2):346–52. doi:10.​1016/​j.​intimp.​2014.​12.​030.PubMed
204.
Zurück zum Zitat Karasneh J, Bani-Hani M, Alkhateeb A, Hassan A, Alzoubi F, Thornhill M. TLR2, TLR4 and CD86 gene polymorphisms in recurrent aphthous stomatitis. J Oral Pathol Med. 2014;. doi:10.1111/jop.12298. Karasneh J, Bani-Hani M, Alkhateeb A, Hassan A, Alzoubi F, Thornhill M. TLR2, TLR4 and CD86 gene polymorphisms in recurrent aphthous stomatitis. J Oral Pathol Med. 2014;. doi:10.​1111/​jop.​12298.
205.
Zurück zum Zitat Alvarez-Rodriguez L, Munoz Cacho P, Lopez-Hoyos M, Beares I, Mata C, Calvo-Alen J, et al. Toll-like receptor 4 gene polymorphism and giant cell arteritis susceptibility: a cumulative meta-analysis. Autoimmun Rev. 2011;10(12):790–2. doi:10.1016/j.autrev.2011.06.002.PubMed Alvarez-Rodriguez L, Munoz Cacho P, Lopez-Hoyos M, Beares I, Mata C, Calvo-Alen J, et al. Toll-like receptor 4 gene polymorphism and giant cell arteritis susceptibility: a cumulative meta-analysis. Autoimmun Rev. 2011;10(12):790–2. doi:10.​1016/​j.​autrev.​2011.​06.​002.PubMed
207.
209.
Zurück zum Zitat Lorenz E, Hallman M, Marttila R, Haataja R, Schwartz DA. Association between the Asp299Gly polymorphisms in the Toll-like receptor 4 and premature births in the finnish population. Pediatr Res. 2002;52(3):373–6. doi:10.1203/00006450-200209000-00011.PubMed Lorenz E, Hallman M, Marttila R, Haataja R, Schwartz DA. Association between the Asp299Gly polymorphisms in the Toll-like receptor 4 and premature births in the finnish population. Pediatr Res. 2002;52(3):373–6. doi:10.​1203/​00006450-200209000-00011.PubMed
210.
Zurück zum Zitat Radstake TR, Franke B, Hanssen S, Netea MG, Welsing P, Barrera P, et al. The Toll-like receptor 4 Asp299Gly functional variant is associated with decreased rheumatoid arthritis disease susceptibility but does not influence disease severity and/or outcome. Arthritis Rheum. 2004;50(3):999–1001. doi:10.1002/art.20114.PubMed Radstake TR, Franke B, Hanssen S, Netea MG, Welsing P, Barrera P, et al. The Toll-like receptor 4 Asp299Gly functional variant is associated with decreased rheumatoid arthritis disease susceptibility but does not influence disease severity and/or outcome. Arthritis Rheum. 2004;50(3):999–1001. doi:10.​1002/​art.​20114.PubMed
211.
Zurück zum Zitat Torok HP, Glas J, Tonenchi L, Mussack T, Folwaczny C. Polymorphisms of the lipopolysaccharide-signaling complex in inflammatory bowel disease: association of a mutation in the Toll-like receptor 4 gene with ulcerative colitis. Clin Immunol. 2004;112(1):85–91. doi:10.1016/j.clim.2004.03.002.PubMed Torok HP, Glas J, Tonenchi L, Mussack T, Folwaczny C. Polymorphisms of the lipopolysaccharide-signaling complex in inflammatory bowel disease: association of a mutation in the Toll-like receptor 4 gene with ulcerative colitis. Clin Immunol. 2004;112(1):85–91. doi:10.​1016/​j.​clim.​2004.​03.​002.PubMed
212.
Zurück zum Zitat Rudofsky G Jr, Reismann P, Witte S, Humpert PM, Isermann B, Chavakis T, et al. Asp299Gly and Thr399Ile genotypes of the TLR4 gene are associated with a reduced prevalence of diabetic neuropathy in patients with type 2 diabetes. Diabetes Care. 2004;27(1):179–83.PubMed Rudofsky G Jr, Reismann P, Witte S, Humpert PM, Isermann B, Chavakis T, et al. Asp299Gly and Thr399Ile genotypes of the TLR4 gene are associated with a reduced prevalence of diabetic neuropathy in patients with type 2 diabetes. Diabetes Care. 2004;27(1):179–83.PubMed
213.
Zurück zum Zitat Yamamoto M, Sato S, Hemmi H, Sanjo H, Uematsu S, Kaisho T, et al. Essential role for TIRAP in activation of the signalling cascade shared by TLR2 and TLR4. Nature. 2002;420(6913):324–9. doi:10.1038/Nature01182.PubMed Yamamoto M, Sato S, Hemmi H, Sanjo H, Uematsu S, Kaisho T, et al. Essential role for TIRAP in activation of the signalling cascade shared by TLR2 and TLR4. Nature. 2002;420(6913):324–9. doi:10.​1038/​Nature01182.PubMed
214.
Zurück zum Zitat Horng T, Barton GM, Flavell RA, Medzhitov R. The adaptor molecule TIRAP provides signalling specificity for Toll-like receptors. Nature. 2002;420(6913):329–33. doi:10.1038/Nature01180.PubMed Horng T, Barton GM, Flavell RA, Medzhitov R. The adaptor molecule TIRAP provides signalling specificity for Toll-like receptors. Nature. 2002;420(6913):329–33. doi:10.​1038/​Nature01180.PubMed
216.
Zurück zum Zitat Dunne A, Ejdeback M, Ludidi PL, O’Neill LAJ, Gay NJ. Structural complementarity of Toll/interleukin-1 receptor domains in Toll-like receptors and the adaptors Mal and MyD88. J Biol Chem. 2003;278(42):41443–51. doi:10.1074/jbc.M301742200.PubMed Dunne A, Ejdeback M, Ludidi PL, O’Neill LAJ, Gay NJ. Structural complementarity of Toll/interleukin-1 receptor domains in Toll-like receptors and the adaptors Mal and MyD88. J Biol Chem. 2003;278(42):41443–51. doi:10.​1074/​jbc.​M301742200.PubMed
217.
Zurück zum Zitat Vogel SN, Fitzgerald KA, Fenton MJ. TLRs: differential adapter utilization by Toll-like receptors mediates TLR-specific patterns of gene expression. Mol Interv. 2003;3(8):466–77. doi:10.1124/mi.3.8.466.PubMed Vogel SN, Fitzgerald KA, Fenton MJ. TLRs: differential adapter utilization by Toll-like receptors mediates TLR-specific patterns of gene expression. Mol Interv. 2003;3(8):466–77. doi:10.​1124/​mi.​3.​8.​466.PubMed
218.
Zurück zum Zitat Jeyaseelan S, Manzer R, Young SK, Yamamoto M, Akira S, Mason RJ, et al. Toll-IL-1 receptor domain-containing adaptor protein is critical for early lung immune responses against Escherichia coli lipopolysaccharide and viable Escherichia coli. J Immunol. 2005;175(11):7484–95.PubMed Jeyaseelan S, Manzer R, Young SK, Yamamoto M, Akira S, Mason RJ, et al. Toll-IL-1 receptor domain-containing adaptor protein is critical for early lung immune responses against Escherichia coli lipopolysaccharide and viable Escherichia coli. J Immunol. 2005;175(11):7484–95.PubMed
219.
Zurück zum Zitat Jeyaseelan S, Young SK, Yamamoto M, Arndt PG, Akira S, Kolls JK, et al. Toll/IL-1R domain-containing adaptor protein (TIRAP) is a critical mediator of antibacterial defense in the lung against Klebsiella pneumoniae but not Pseudomonas aeruginosa. J Immunol. 2006;177(1):538–47.PubMed Jeyaseelan S, Young SK, Yamamoto M, Arndt PG, Akira S, Kolls JK, et al. Toll/IL-1R domain-containing adaptor protein (TIRAP) is a critical mediator of antibacterial defense in the lung against Klebsiella pneumoniae but not Pseudomonas aeruginosa. J Immunol. 2006;177(1):538–47.PubMed
220.
Zurück zum Zitat Khor CC, Chapman SJ, Vannberg FO, Dunne A, Murphy C, Ling EY, et al. A Mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis. Nat Genet. 2007;39(4):523–8. doi:10.1038/Ng1976.PubMedCentralPubMed Khor CC, Chapman SJ, Vannberg FO, Dunne A, Murphy C, Ling EY, et al. A Mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis. Nat Genet. 2007;39(4):523–8. doi:10.​1038/​Ng1976.PubMedCentralPubMed
221.
Zurück zum Zitat Mansell A, Brint E, Gould JA, O’Neill LA, Hertzog PJ. Mal interacts with tumor necrosis factor receptor-associated factor (TRAF)-6 to mediate NF-κB activation by Toll-like receptor (TLR)-2 and TLR4. J Biol Chem. 2004;279(36):37227–30. doi:10.1074/jbc.C400289200.PubMed Mansell A, Brint E, Gould JA, O’Neill LA, Hertzog PJ. Mal interacts with tumor necrosis factor receptor-associated factor (TRAF)-6 to mediate NF-κB activation by Toll-like receptor (TLR)-2 and TLR4. J Biol Chem. 2004;279(36):37227–30. doi:10.​1074/​jbc.​C400289200.PubMed
222.
Zurück zum Zitat Castiblanco J, Varela DC, Castano-Rodriguez N, Rojas-Villarraga A, Hincape ME, Anaya JM. TIRAP (MAL) S180L polymorphism is a common protective factor against developing tuberculosis and systemic lupus erythematosus. Infect Genet Evol. 2008;8(5):541–4. doi:10.1016/j.meegid.2008.03.001.PubMed Castiblanco J, Varela DC, Castano-Rodriguez N, Rojas-Villarraga A, Hincape ME, Anaya JM. TIRAP (MAL) S180L polymorphism is a common protective factor against developing tuberculosis and systemic lupus erythematosus. Infect Genet Evol. 2008;8(5):541–4. doi:10.​1016/​j.​meegid.​2008.​03.​001.PubMed
223.
Zurück zum Zitat Dissanayeke SR, Levin S, Pienaar S, Wood K, Eley B, Beatty D, et al. Polymorphic variation in TIRAP is not associated with susceptibility to childhood TB but may determine susceptibility to TBM in some ethnic groups. PLoS One. 2009;4(8):e6698. doi:10.1371/journal.pone.0006698.PubMedCentralPubMed Dissanayeke SR, Levin S, Pienaar S, Wood K, Eley B, Beatty D, et al. Polymorphic variation in TIRAP is not associated with susceptibility to childhood TB but may determine susceptibility to TBM in some ethnic groups. PLoS One. 2009;4(8):e6698. doi:10.​1371/​journal.​pone.​0006698.PubMedCentralPubMed
224.
Zurück zum Zitat Selvaraj P, Harishankar M, Singh B, Jawahar MS, Banurekha VV. Toll-like receptor and TIRAP gene polymorphisms in pulmonary tuberculosis patients of South India. Tuberculosis (Edinb). 2010;90(5):306–10. doi:10.1016/j.tube.2010.08.001. Selvaraj P, Harishankar M, Singh B, Jawahar MS, Banurekha VV. Toll-like receptor and TIRAP gene polymorphisms in pulmonary tuberculosis patients of South India. Tuberculosis (Edinb). 2010;90(5):306–10. doi:10.​1016/​j.​tube.​2010.​08.​001.
225.
Zurück zum Zitat Nejentsev S, Thye T, Szeszko JS, Stevens H, Balabanova Y, Chinbuah AM, et al. Analysis of association of the TIRAP (MAL) S180L variant and tuberculosis in three populations. Nat Genet. 2008;40(3):261–2. doi:10.1038/Ng0308-261.PubMed Nejentsev S, Thye T, Szeszko JS, Stevens H, Balabanova Y, Chinbuah AM, et al. Analysis of association of the TIRAP (MAL) S180L variant and tuberculosis in three populations. Nat Genet. 2008;40(3):261–2. doi:10.​1038/​Ng0308-261.PubMed
226.
227.
Zurück zum Zitat Hawn TR, Dunstan SJ, Thwaites GE, Simmons CP, Thuong NT, Lan NTN, et al. A polymorphism in Toll-interleukin 1 receptor domain containing adaptor protein is associated with susceptibility to meningeal tuberculosis. J Infect Dis. 2006;194(8):1127–34. doi:10.1086/507907.PubMedCentralPubMed Hawn TR, Dunstan SJ, Thwaites GE, Simmons CP, Thuong NT, Lan NTN, et al. A polymorphism in Toll-interleukin 1 receptor domain containing adaptor protein is associated with susceptibility to meningeal tuberculosis. J Infect Dis. 2006;194(8):1127–34. doi:10.​1086/​507907.PubMedCentralPubMed
228.
Zurück zum Zitat Zhang YX, Xue Y, Liu JY, Zhao MY, Li FJ, Zhou JM, et al. Association of TIRAP (MAL) gene polymorphisms with susceptibility to tuberculosis in a Chinese population. Genet Mol Res. 2011;10(1):7–15. doi:10.4238/vol10-1gmr980.PubMed Zhang YX, Xue Y, Liu JY, Zhao MY, Li FJ, Zhou JM, et al. Association of TIRAP (MAL) gene polymorphisms with susceptibility to tuberculosis in a Chinese population. Genet Mol Res. 2011;10(1):7–15. doi:10.​4238/​vol10-1gmr980.PubMed
229.
230.
Zurück zum Zitat Ferwerda B, Alonso S, Banahan K, McCall MBB, Giamarellos-Bourboulis EJ, Ramakers BP, et al. Functional and genetic evidence that the Mal/TIRAP allele variant 180L has been selected by providing protection against septic shock. Proce Natl Acad Sci USA. 2009;106(25):10272–7. doi:10.1073/pnas.0811273106. Ferwerda B, Alonso S, Banahan K, McCall MBB, Giamarellos-Bourboulis EJ, Ramakers BP, et al. Functional and genetic evidence that the Mal/TIRAP allele variant 180L has been selected by providing protection against septic shock. Proce Natl Acad Sci USA. 2009;106(25):10272–7. doi:10.​1073/​pnas.​0811273106.
231.
Zurück zum Zitat Song ZJ, Tong CY, Sun Z, Shen Y, Yao CL, Jiang JJ, et al. Genetic variants in the TIRAP gene are associated with increased risk of sepsis-associated acute lung injury. Bmc Med Genet. 2010;. doi:10.1186/1471-2350-11-168. Song ZJ, Tong CY, Sun Z, Shen Y, Yao CL, Jiang JJ, et al. Genetic variants in the TIRAP gene are associated with increased risk of sepsis-associated acute lung injury. Bmc Med Genet. 2010;. doi:10.​1186/​1471-2350-11-168.
233.
Zurück zum Zitat Esposito S, Molteni CG, Zampiero A, Baggi E, Lavizzari A, Semino M, et al. Role of polymorphisms of Toll-like receptor (TLR) 4, TLR9, Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) and FCGR2A genes in malaria susceptibility and severity in Burundian children. Malar J. 2012;11:196. doi:10.1186/1475-2875-11-196.PubMedCentralPubMed Esposito S, Molteni CG, Zampiero A, Baggi E, Lavizzari A, Semino M, et al. Role of polymorphisms of Toll-like receptor (TLR) 4, TLR9, Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) and FCGR2A genes in malaria susceptibility and severity in Burundian children. Malar J. 2012;11:196. doi:10.​1186/​1475-2875-11-196.PubMedCentralPubMed
234.
Zurück zum Zitat Ramasawmy R, Cunha-Neto E, Fae KC, Borba SCP, Teixeira PC, Ferreira SCP, et al. Heterozygosity for the S180L Variant of MAL/TIRAP, a gene expressing an adaptor protein in the Toll-like receptor pathway, is associated with lower risk of developing chronic chagas cardiomyopathy. J Infect Dis. 2009;199(12):1838–45. doi:10.1086/599212.PubMed Ramasawmy R, Cunha-Neto E, Fae KC, Borba SCP, Teixeira PC, Ferreira SCP, et al. Heterozygosity for the S180L Variant of MAL/TIRAP, a gene expressing an adaptor protein in the Toll-like receptor pathway, is associated with lower risk of developing chronic chagas cardiomyopathy. J Infect Dis. 2009;199(12):1838–45. doi:10.​1086/​599212.PubMed
235.
Zurück zum Zitat Durrani O, Banahan K, Sheedy FJ, McBride L, Ben-Chetrit E, Greiner K, et al. TIRAP Ser180Leu polymorphism is associated with Behcet’s disease. Rheumatology (Oxford). 2011;50(10):1760–5. doi:10.1093/rheumatology/ker200. Durrani O, Banahan K, Sheedy FJ, McBride L, Ben-Chetrit E, Greiner K, et al. TIRAP Ser180Leu polymorphism is associated with Behcet’s disease. Rheumatology (Oxford). 2011;50(10):1760–5. doi:10.​1093/​rheumatology/​ker200.
236.
Zurück zum Zitat Moser KL, Neas BR, Salmon JE, Yu H, Gray-McGuire C, Asundi N, et al. Genome scan of human systemic lupus erythematosus: Evidence for linkage on chromosome 1q in African–American pedigrees. Proc Natl Acad Sci USA. 1998;95(25):14869–74. doi:10.1073/pnas.95.25.14869.PubMedCentralPubMed Moser KL, Neas BR, Salmon JE, Yu H, Gray-McGuire C, Asundi N, et al. Genome scan of human systemic lupus erythematosus: Evidence for linkage on chromosome 1q in African–American pedigrees. Proc Natl Acad Sci USA. 1998;95(25):14869–74. doi:10.​1073/​pnas.​95.​25.​14869.PubMedCentralPubMed
237.
Zurück zum Zitat Lindqvist AKB, Steinsson K, Johanneson B, Kristjansdottir H, Arnasson A, Grondal G, et al. A susceptibility locus for human systemic lupus erythematosus (hSLE1) on chromosome 2q. J Autoimmun. 2000;14(2):169–78. doi:10.1006/jaut.1999.0357.PubMed Lindqvist AKB, Steinsson K, Johanneson B, Kristjansdottir H, Arnasson A, Grondal G, et al. A susceptibility locus for human systemic lupus erythematosus (hSLE1) on chromosome 2q. J Autoimmun. 2000;14(2):169–78. doi:10.​1006/​jaut.​1999.​0357.PubMed
238.
Zurück zum Zitat Rupasree Y, Naushad S, Rajasekhar L, Uma A, Kutala V. Association of TLR4 (D299G, T399I), TLR9 -1486T > C, TIRAP S180L and TNF-alpha promoter (-1031, -863, -857) polymorphisms with risk for systemic lupus erythematosus among South Indians. Lupus. 2014;. doi:10.1177/0961203314549792.PubMed Rupasree Y, Naushad S, Rajasekhar L, Uma A, Kutala V. Association of TLR4 (D299G, T399I), TLR9 -1486T > C, TIRAP S180L and TNF-alpha promoter (-1031, -863, -857) polymorphisms with risk for systemic lupus erythematosus among South Indians. Lupus. 2014;. doi:10.​1177/​0961203314549792​.PubMed
239.
Zurück zum Zitat Sheedy FJ, Marinou I, O’Neill LAJ, Wilson AG. The Mal/TIRAP S180L and TLR4 G299D polymorphisms are not associated with susceptibility to, or severity of, rheumatoid arthritis. Ann Rheum Dis. 2008;67(9):1328–31. doi:10.1136/ard.2007.083337.PubMed Sheedy FJ, Marinou I, O’Neill LAJ, Wilson AG. The Mal/TIRAP S180L and TLR4 G299D polymorphisms are not associated with susceptibility to, or severity of, rheumatoid arthritis. Ann Rheum Dis. 2008;67(9):1328–31. doi:10.​1136/​ard.​2007.​083337.PubMed
240.
Zurück zum Zitat Cantaert T, Stone M, ter Borg M, de Vries N, Wilson A, Tak P, et al. A functional variant of TIR-domain-containing adaptor protein (TIRAP) is not associated with spondyloarthritis. Clin Immunol. 2008;127:S85. doi:10.1016/j.clim.2008.03.238. Cantaert T, Stone M, ter Borg M, de Vries N, Wilson A, Tak P, et al. A functional variant of TIR-domain-containing adaptor protein (TIRAP) is not associated with spondyloarthritis. Clin Immunol. 2008;127:S85. doi:10.​1016/​j.​clim.​2008.​03.​238.
Metadaten
Titel
Association of TLR1, TLR2, TLR4, TLR6, and TIRAP polymorphisms with disease susceptibility
verfasst von
Mamoona Noreen
Muhammad Arshad
Publikationsdatum
01.06.2015
Verlag
Springer US
Erschienen in
Immunologic Research / Ausgabe 2/2015
Print ISSN: 0257-277X
Elektronische ISSN: 1559-0755
DOI
https://doi.org/10.1007/s12026-015-8640-6

Weitere Artikel der Ausgabe 2/2015

Immunologic Research 2/2015 Zur Ausgabe

Akuter Schwindel: Wann lohnt sich eine MRT?

28.04.2024 Schwindel Nachrichten

Akuter Schwindel stellt oft eine diagnostische Herausforderung dar. Wie nützlich dabei eine MRT ist, hat eine Studie aus Finnland untersucht. Immerhin einer von sechs Patienten wurde mit akutem ischämischem Schlaganfall diagnostiziert.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

HNO-Op. auch mit über 90?

16.04.2024 HNO-Chirurgie Nachrichten

Mit Blick auf das Risiko für Komplikationen nach elektiven Eingriffen im HNO-Bereich scheint das Alter der Patienten kein ausschlaggebender Faktor zu sein. Entscheidend ist offenbar, wie fit die Betroffenen tatsächlich sind.

Intrakapsuläre Tonsillektomie gewinnt an Boden

16.04.2024 Tonsillektomie Nachrichten

Gegenüber der vollständigen Entfernung der Gaumenmandeln hat die intrakapsuläre Tonsillektomie einige Vorteile, wie HNO-Fachleute aus den USA hervorheben. Sie haben die aktuelle Literatur zu dem Verfahren gesichtet.

Update HNO

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.