Skip to main content

Advertisement

SpringerLink
Log in

Modulation of γδ T cell responses by TLR ligands

  • Multi-author review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

Toll-like receptors (TLR) are pattern-recognition receptors that recognize a broad variety of structurally conserved molecules derived from microbes. The recognition of TLR ligands functions as a primary sensor of the innate immune system, leading to subsequent indirect activation of the adaptive immunity as well as none-immune cells. However, TLR are also expressed by several T cell subsets, and the respective ligands can directly modulate their effector functions. The present review summarizes the recent findings of γδ T cell modulation by TLR ligands. TLR1/2/6, 3, and 5 ligands can act directly in combination with T cell receptor (TCR) stimulation to enhance cytokine/chemokine production of freshly isolated human γδ T cells. In contrast to human γδ T cells, murine and bovine γδ T cells can directly respond to TLR2 ligands with increased proliferation and cytokine production in a TCR-independent manner. Indirect stimulatory effects on IFN-γ production of human and murine γδ T cells via TLR-ligand activated dendritic cells have been described for TLR2, 3, 4, 7, and 9 ligands. In addition, TLR3 and 7 ligands indirectly increase tumor cell lysis by human γδ T cells, whereas ligation of TLR8 abolishes the suppressive activity of human tumor-infiltrating Vδ1 γδ T cells on αβ T cells and dendritic cells. Taken together, these data suggest that TLR-mediated signals received by γδ T cells enhance the initiation of adaptive immune responses during bacterial and viral infection directly or indirectly. Moreover, TLR ligands enhance cytotoxic tumor responses of γδ T cells and regulate the suppressive capacity of γδ T cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Hayday AC (2000) γδ cells: a right time and a right place for a conserved third way of protection. Annu Rev Immunol 18:975–1026

    Article  PubMed  CAS  Google Scholar 

  2. Kabelitz D, Glatzel A, Wesch D (2000) Antigen recognition by human γδ T lymphocytes. Int Arch Allergy Immunol 122:1–7

    Article  PubMed  CAS  Google Scholar 

  3. Kabelitz D, Marischen L, Oberg HH, Holtmeier W, Wesch D (2005) Epithelial defence by γδ T cells. Int Arch Allergy Immunol 137:73–81

    Article  PubMed  CAS  Google Scholar 

  4. Wesch D, Marischen L, Kabelitz D (2005) Regulation of cytokine production by γδ T cells. Curr Med Chem Anti-Inflamm Anti-Allergy Agents 4:153–160

    Article  CAS  Google Scholar 

  5. Hintz M, Reichenberg A, Altincicek B, Bahr U, Gschwind RM, Kollas AK, Beck E, Wiesner J, Eberl M, Jomaa H (2001) Identification of (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate as a major activator for human γδ T cells in Escherichia coli. FEBS Lett 509:317–322

    Article  PubMed  CAS  Google Scholar 

  6. Groh V, Steinle A, Bauer S, Spies T (1998) Recognition of stress-induced MHC molecules by intestinal epithelial γδ T cells. Science 279:1737–1740

    Article  PubMed  CAS  Google Scholar 

  7. Spada FM, Grant EP, Peters PJ, Sugita M, Melian A, Leslie DS, Lee HK, van Donsellar E, Hanson DA, Krensky AM, Majdic O, Porcelli SA, Morita CT, Brenner MB (2000) Self-recognition of CD1 by γδ T cells: implications for innate immunity. J Exp Med 191:937–948

    Google Scholar 

  8. Heilig JS, Tonegawa S (1986) Diversity of murine γ genes and expression in fetal and adult T lymphocytes. Nature 322:836–840

    Article  PubMed  CAS  Google Scholar 

  9. Bonneville M, O’Brien RL, Born WK (2010) γδ T cell effector functions: a blend of innate programming and acquired plasticity. Nat Rev Immunol 10:467–478

    Article  PubMed  CAS  Google Scholar 

  10. Born WK, Yin Z, Hahn YS, Sun D, O’Brien RL (2010) Analysis of γδ T cell functions in the mouse. J Immunol 184:4055–4061

    Article  PubMed  CAS  Google Scholar 

  11. Chang ZL (2010) Important aspects of Toll-like receptors, ligands and their signaling pathways. Inflamm Res 59:791–808

    Article  PubMed  CAS  Google Scholar 

  12. Kawai T, Akira S (2010) The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 11:373–384

    Article  PubMed  CAS  Google Scholar 

  13. Kabelitz D, Wesch D, Oberg HH (2006) Regulation of regulatory T cells: role of dendritic cells and Toll-like receptors. Crit Rev Immunol 26:291–306

    PubMed  CAS  Google Scholar 

  14. Kabelitz D (2007) Expression and function of Toll-like receptors in T lymphocytes. Curr Opin Immunol 19:39–45

    Article  PubMed  CAS  Google Scholar 

  15. Kulkarni R, Behboudi S, Sharif S (2011) Insights into the role of Toll-like receptors in modulation of T cell responses. Cell Tissue Res 343:141–152

    Article  PubMed  CAS  Google Scholar 

  16. Pietschmann K, Beetz S, Welte S, Martens I, Gruen J, Oberg HH, Wesch D, Kabelitz D (2009) Toll-like receptor expression and function in subsets of human γδ T lymphocytes. Scand J Immunol 70:245–255

    Article  PubMed  CAS  Google Scholar 

  17. Wesch D, Beetz S, Oberg HH, Marget M, Krengel K, Kabelitz D (2006) Direct costimulatory effect of TLR3 ligand poly(I:C) on human γδ T lymphocytes. J Immunol 176:1348–1354

    PubMed  CAS  Google Scholar 

  18. Belvin MP, Anderson KV (1996) A conserved signaling pathway: the Drosophila Toll-dorsal pathway. Annu Rev Cell Dev Biol 12:393–416

    Article  PubMed  CAS  Google Scholar 

  19. Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA (1996) The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 86:973–983

    Article  PubMed  CAS  Google Scholar 

  20. Medzhitov R, Preston-Hurlburt P, Janeway CA Jr (1997) A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388:394–397

    Article  PubMed  CAS  Google Scholar 

  21. Kawai T, Akira S (2009) The roles of TLRs, RLRs and NLRs in pathogen recognition. Int Immunol 21:317–337

    Article  PubMed  CAS  Google Scholar 

  22. Kumar H, Kawai T, Akira S (2009) Toll-like receptors and innate immunity. Biochem Biophys Res Commun 388:621–625

    Article  PubMed  CAS  Google Scholar 

  23. Matsushima N, Tanaka T, Enkhbayar P, Mikami T, Taga M, Yamada K, Kuroki Y (2007) Comparative sequence analysis of leucine-rich repeats (LRRs) within vertebrate Toll-like receptors. BMC Genomics 8:124

    Article  PubMed  CAS  Google Scholar 

  24. O’Neill LA, Bowie AG (2007) The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat Rev Immunol 7:353–364

    Article  PubMed  CAS  Google Scholar 

  25. Kawai T, Akira S (2007) TLR signaling. Semin Immunol 19:24–32

    Article  PubMed  CAS  Google Scholar 

  26. Akira S, Uematsu S, Takeuchi O (2006) Pathogen recognition and innate immunity. Cell 124:783–801

    Article  PubMed  CAS  Google Scholar 

  27. Kim YM, Brinkmann MM, Paquet ME, Ploegh HL (2008) UNC93B1 delivers nucleotide-sensing Toll-like receptors to endolysosomes. Nature 452:234–238

    Article  PubMed  CAS  Google Scholar 

  28. Takahashi K, Shibata T, Akashi-Takamura S, Kiyokawa T, Wakabayashi Y, Tanimura N, Kobayashi T, Matsumoto F, Fukui R, Kouro T, Nagai Y, Takatsu K, Saitoh S, Miyake K (2007) A protein associated with Toll-like receptor (TLR) 4 (PRAT4A) is required for TLR-dependent immune responses. J Exp Med 204:2963–2976

    Article  PubMed  CAS  Google Scholar 

  29. O’Neill LA, Bryant CE, Doyle SL (2009) Therapeutic targeting of Toll-like receptors for infectious and inflammatory diseases and cancer. Pharmacol Rev 61:177–197

    Article  PubMed  CAS  Google Scholar 

  30. Warshakoon HJ, Hood JD, Kimbrell MR, Malladi S, Wu WY, Shukla NM, Agnihotri G, Sil D, David SA (2009) Potential adjuvantic properties of innate immune stimuli. Hum Vaccin 5:381–394

    PubMed  CAS  Google Scholar 

  31. Coats SR, Pham TT, Bainbridge BW, Reife RA, Darveau RP (2005) MD-2 mediates the ability of tetra-acylated and penta-acylated lipopolysaccharides to antagonize Escherichia coli lipopolysaccharide at the TLR4 signaling complex. J Immunol 175:4490–4498

    PubMed  CAS  Google Scholar 

  32. Gursel I, Gursel M, Yamada H, Ishii KJ, Takeshita F, Klinman DM (2003) Repetitive elements in mammalian telomeres suppress bacterial DNA-induced immune activation. J Immunol 171:1393–1400

    PubMed  CAS  Google Scholar 

  33. Hornung V, Rothenfusser S, Britsch S, Krug A, Jahrsdorfer B, Giese T, Endres S, Hartmann G (2002) Quantitative expression of Toll-like receptor 1–10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides. J Immunol 168:4531–4537

    PubMed  CAS  Google Scholar 

  34. Deetz CO, Hebbeler AM, Propp NA, Cairo C, Tikhonov I, Pauza CD (2006) Gamma interferon secretion by human Vγ2 Vδ2 T cells after stimulation with antibody against the T-cell receptor plus the Toll-like receptor 2 agonist Pam3Cys. Infect Immun 74:4505–4511

    Article  PubMed  CAS  Google Scholar 

  35. Devilder MC, Allain S, Dousset C, Bonneville M, Scotet E (2009) Early triggering of exclusive IFN-gamma responses of human Vγ9Vδ2 T cells by TLR-activated myeloid and plasmacytoid dendritic cells. J Immunol 183:3625–3633

    Article  PubMed  CAS  Google Scholar 

  36. Hedges JF, Lubick KJ, Jutila MA (2005) γδ T cells respond directly to pathogen-associated molecular patterns. J Immunol 174:6045–6053

    PubMed  CAS  Google Scholar 

  37. Ohnesorge S, Oberg HH, Peters C, Janssen O, Kabelitz D, Wesch D (2009) Differential poly(I:C) responses of human Vγ9Vδ2 T cells stimulated with pyrophosphates versus aminobisphosphonates. Open Immuol J 2:135–142

    Article  CAS  Google Scholar 

  38. Beetz S, Wesch D, Marischen L, Welte S, Oberg HH, Kabelitz D (2008) Innate immune functions of human γδ T cells. Immunobiology 213:173–182

    Article  PubMed  CAS  Google Scholar 

  39. Cui Y, Kang L, Cui L, He W (2009) Human γδ T cell recognition of lipid A is predominately presented by CD1b or CD1c on dendritic cells. Biol Direct 4:1–12

    Article  CAS  Google Scholar 

  40. Kunzmann V, Kretzschmar E, Herrmann T, Wilhelm M (2004) Polyinosinic-polycytidylic acid-mediated stimulation of human γδ T cells via CD11c dendritic cell-derived type I interferons. Immunology 112:369–377

    Article  PubMed  CAS  Google Scholar 

  41. Rothenfusser S, Hornung V, Krug A, Towarowski A, Krieg AM, Endres S, Hartmann G (2001) Distinct CpG oligonucleotide sequences activate human γδ T cells via interferon-alpha/-beta. Eur J Immunol 31:3525–3534

    Article  PubMed  CAS  Google Scholar 

  42. Shrestha N, Ida JA, Lubinski AS, Pallin M, Kaplan G, Haslett PA (2005) Regulation of acquired immunity by γδ T-cell/dendritic-cell interactions. Ann N Y Acad Sci 1062:79–94

    Article  PubMed  CAS  Google Scholar 

  43. Shojaei H, Oberg HH, Juricke M, Marischen L, Kunz M, Mundhenke C, Gieseler F, Kabelitz D, Wesch D (2009) Toll-like receptors 3 and 7 agonists enhance tumor cell lysis by human γδ T cells. Cancer Res 69:8710–8717

    Article  PubMed  CAS  Google Scholar 

  44. Gibbons DL, Haque SF, Silberzahn T, Hamilton K, Langford C, Ellis P, Carr R, Hayday AC (2009) Neonates harbour highly active γδ T cells with selective impairments in preterm infants. Eur J Immunol 39:1794–1806

    Article  PubMed  CAS  Google Scholar 

  45. Collins C, Shi C, Russell JQ, Fortner KA, Budd RC (2008) Activation of γδ T cells by Borrelia burgdorferi is indirect via a TLR- and caspase-dependent pathway. J Immunol 181:2392–2398

    PubMed  CAS  Google Scholar 

  46. Peng G, Wang HY, Peng W, Kiniwa Y, Seo KH, Wang RF (2007) Tumor-infiltrating γδ T cells suppress T and dendritic cell function via mechanisms controlled by a unique Toll-like receptor signaling pathway. Immunity 27:334–348

    Article  PubMed  CAS  Google Scholar 

  47. Buwitt-Beckmann U, Heine H, Wiesmuller KH, Jung G, Brock R, Ulmer AJ (2005) Lipopeptide structure determines TLR2-dependent cell activation level. FEBS J 272:6354–6364

    Article  PubMed  CAS  Google Scholar 

  48. Dziarski R, Gupta D (2006) The peptidoglycan recognition proteins (PGRPs). Genome Biol 7:232–245

    Article  PubMed  CAS  Google Scholar 

  49. Schroder NW, Morath S, Alexander C, Hamann L, Hartung T, Zahringer U, Gobel UB, Weber JR, Schumann RR (2003) Lipoteichoic acid (LTA) of Streptococcus pneumoniae and Staphylococcus aureus activates immune cells via Toll-like receptor (TLR)-2, lipopolysaccharide-binding protein (LBP), and CD14, whereas TLR-4 and MD-2 are not involved. J Biol Chem 278:15587–15594

    Article  PubMed  Google Scholar 

  50. Hasan U, Chaffois C, Gaillard C, Saulnier V, Merck E, Tancredi S, Guiet C, Briere F, Vlach J, Lebecque S, Trinchieri G, Bates EE (2005) Human TLR10 is a functional receptor, expressed by B cells and plasmacytoid dendritic cells, which activates gene transcription through MyD88. J Immunol 174:2942–2950

    PubMed  CAS  Google Scholar 

  51. Hoebe K, Georgel P, Rutschmann S, Du X, Mudd S, Crozat K, Sovath S, Shamel L, Hartung T, Zahringer U, Beutler B (2005) CD36 is a sensor of diacylglycerides. Nature 433:523–527

    Article  PubMed  CAS  Google Scholar 

  52. Melkamu T, Squillace D, Kita H, O’Grady SM (2009) Regulation of TLR2 expression and function in human airway epithelial cells. J Membr Biol 229:101–113

    Article  PubMed  CAS  Google Scholar 

  53. Buwitt-Beckmann U, Heine H, Wiesmuller KH, Jung G, Brock R, Akira S, Ulmer AJ (2005) Toll-like receptor 6-independent signaling by diacylated lipopeptides. Eur J Immunol 35:282–289

    Article  PubMed  CAS  Google Scholar 

  54. Hajjar AM, O’Mahony DS, Ozinsky A, Underhill DM, Aderem A, Klebanoff SJ, Wilson CB (2001) Cutting edge: functional interactions between Toll-like receptor (TLR) 2 and TLR1 or TLR6 in response to phenol-soluble modulin. J Immunol 166:15–19

    PubMed  CAS  Google Scholar 

  55. Okusawa T, Fujita M, Nakamura J, Into T, Yasuda M, Yoshimura A, Hara Y, Hasebe A, Golenbock DT, Morita M, Kuroki Y, Ogawa T, Shibata K (2004) Relationship between structures and biological activities of mycoplasmal diacylated lipopeptides and their recognition by Toll-like receptors 2 and 6. Infect Immun 72:1657–1665

    Article  PubMed  CAS  Google Scholar 

  56. Takeuchi O, Kawai T, Muhlradt PF, Morr M, Radolf JD, Zychlinsky A, Takeda K, Akira S (2001) Discrimination of bacterial lipoproteins by Toll-like receptor 6. Int Immunol 13:933–940

    Article  PubMed  CAS  Google Scholar 

  57. Rose WA, McGowin CL, Pyles RB (2009) FSL-1, a bacterial-derived Toll-like receptor 2/6 agonist, enhances resistance to experimental HSV-2 infection. Virol J 6:195

    Article  PubMed  CAS  Google Scholar 

  58. Lu H, Yang Y, Gad E, Wenner CA, Chang A, Larson ER, Dang Y, Martzen M, Standish LJ, Disis ML (2011) Polysaccharide Krestin is a novel TLR2 agonist that mediates inhibition of tumor growth via stimulation of CD8 T cells and NK cells. Clin Cancer Res 17:67–76

    Google Scholar 

  59. Meng YL, Liu Z, Rosen BP (2004) As(III) and Sb(III) uptake by GlpF and efflux by ArsB in Escherichia coli. J Biol Chem 279:18334–18341

    Article  PubMed  CAS  Google Scholar 

  60. Spiller S, Elson G, Ferstl R, Dreher S, Mueller T, Freudenberg M, Daubeuf B, Wagner H, Kirschning CJ (2008) TLR4-induced IFN-γ production increases TLR2 sensitivity and drives Gram-negative sepsis in mice. J Exp Med 205:1747–1754

    Article  PubMed  CAS  Google Scholar 

  61. Oberg HH, Ly TT, Ussat S, Meyer T, Kabelitz D, Wesch D (2010) Differential but direct abolishment of human regulatory T cell suppressive capacity by various TLR2 ligands. J Immunol 184:4733–4740

    Article  PubMed  CAS  Google Scholar 

  62. Mokuno Y, Matsuguchi T, Takano M, Nishimura H, Washizu J, Ogawa T, Takeuchi O, Akira S, Nimura Y, Yoshikai Y (2000) Expression of Toll-like receptor 2 on γδ T cells bearing invariant V γ 6/V δ 1 induced by Escherichia coli infection in mice. J Immunol 165:931–940

    PubMed  CAS  Google Scholar 

  63. Martin B, Hirota K, Cua DJ, Stockinger B, Veldhoen M (2009) Interleukin-17-producing γδ T cells selectively expand in response to pathogen products and environmental signals. Immunity 31:321–330

    Article  PubMed  CAS  Google Scholar 

  64. Schwacha MG, Daniel T (2008) Up-regulation of cell surface Toll-like receptors on circulating γδ T-cells following burn injury. Cytokine 44:328–334

    Article  PubMed  CAS  Google Scholar 

  65. Li H, Luo K, Pauza CD (2008) TNF-α is a positive regulatory factor for human Vγ2 Vδ2 T cells. J Immunol 181:7131–7137

    PubMed  CAS  Google Scholar 

  66. Takeuchi O, Sato S, Horiuchi T, Hoshino K, Takeda K, Dong Z, Modlin RL, Akira S (2002) Cutting edge: role of Toll-like receptor 1 in mediating immune response to microbial lipoproteins. J Immunol 169:10–14

    PubMed  CAS  Google Scholar 

  67. Lubick K, Jutila MA (2006) LTA recognition by bovine γδ T cells involves CD36. J Leukoc Biol 79:1268–1270

    Article  PubMed  CAS  Google Scholar 

  68. Leclercq G, Plum J (1995) Stimulation of TCR Vγ3 cells by Gram-negative bacteria. J Immunol 154:5313–5319

    PubMed  CAS  Google Scholar 

  69. Toth B, Alexander M, Daniel T, Chaudry IH, Hubbard WJ, Schwacha MG (2004) The role of γδ T cells in the regulation of neutrophil-mediated tissue damage after thermal injury. J Leukoc Biol 76:545–552

    Article  PubMed  CAS  Google Scholar 

  70. Matsushima A, Ogura H, Fujita K, Koh T, Tanaka H, Sumi Y, Yoshiya K, Hosotsubo H, Kuwagata Y, Shimazu T, Sugimoto H (2004) Early activation of γδ T lymphocytes in patients with severe systemic inflammatory response syndrome. Shock 22:11–15

    Article  PubMed  CAS  Google Scholar 

  71. Bochud PY, Hawn TR, Aderem A (2003) Cutting edge: a Toll-like receptor 2 polymorphism that is associated with lepromatous leprosy is unable to mediate mycobacterial signaling. J Immunol 170:3451–3454

    PubMed  CAS  Google Scholar 

  72. Kang TJ, Chae GT (2001) Detection of Toll-like receptor 2 (TLR2) mutation in the lepromatous leprosy patients. FEMS Immunol Med Microbiol 31:53–58

    Article  PubMed  CAS  Google Scholar 

  73. Kang TJ, Lee SB, Chae GT (2002) A polymorphism in the Toll-like receptor 2 is associated with IL-12 production from monocyte in lepromatous leprosy. Cytokine 20:56–62

    Article  PubMed  CAS  Google Scholar 

  74. Krutzik SR, Ochoa MT, Sieling PA, Uematsu S, Ng YW, Legaspi A, Liu PT, Cole ST, Godowski PJ, Maeda Y, Sarno EN, Norgard MV, Brennan PJ, Akira S, Rea TH, Modlin RL (2003) Activation and regulation of Toll-like receptors 2 and 1 in human leprosy. Nat Med 9:525–532

    Article  PubMed  CAS  Google Scholar 

  75. Alexopoulou L, Holt AC, Medzhitov R, Flavell RA (2001) Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3. Nature 413:732–738

    Article  PubMed  CAS  Google Scholar 

  76. Kariko K, Bhuyan P, Capodici J, Weissman D (2004) Small interfering RNAs mediate sequence-independent gene suppression and induce immune activation by signaling through Toll-like receptor 3. J Immunol 172:6545–6549

    PubMed  CAS  Google Scholar 

  77. Bell JK, Askins J, Hall PR, Davies DR, Segal DM (2006) The dsRNA binding site of human Toll-like receptor 3. Proc Natl Acad Sci USA 103:8792–8797

    Article  PubMed  CAS  Google Scholar 

  78. Wang T, Town T, Alexopoulou L, Anderson JF, Fikrig E, Flavell RA (2004) Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis. Nat Med 10:1366–1373

    Article  PubMed  CAS  Google Scholar 

  79. Tabeta K, Georgel P, Janssen E, Du X, Hoebe K, Crozat K, Mudd S, Shamel L, Sovath S, Goode J, Alexopoulou L, Flavell RA, Beutler B (2004) Toll-like receptors 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection. Proc Natl Acad Sci USA 101:3516–3521

    Article  PubMed  CAS  Google Scholar 

  80. Zhang SY, Jouanguy E, Ugolini S, Smahi A, Elain G, Romero P, Segal D, Sancho-Shimizu V, Lorenzo L, Puel A, Picard C, Chapgier A, Plancoulaine S, Titeux M, Cognet C, von BH, Ku CL, Casrouge A, Zhang XX, Barreiro L, Leonard J, Hamilton C, Lebon P, Heron B, Vallee L, Quintana-Murci L, Hovnanian A, Rozenberg F, Vivier E, Geissmann F, Tardieu M, Abel L, Casanova JL (2007) TLR3 deficiency in patients with herpes simplex encephalitis. Science 317:1522–1527

  81. Jasani B, Navabi H, Adams M (2009) Ampligen: a potential Toll-like 3 receptor adjuvant for immunotherapy of cancer. Vaccine 27:3401–3404

    Article  PubMed  CAS  Google Scholar 

  82. Groskreutz DJ, Monick MM, Powers LS, Yarovinsky TO, Look DC, Hunninghake GW (2006) Respiratory syncytial virus induces TLR3 protein and protein kinase R, leading to increased double-stranded RNA responsiveness in airway epithelial cells. J Immunol 176:1733–1740

    PubMed  CAS  Google Scholar 

  83. Hewson CA, Jardine A, Edwards MR, Laza-Stanca V, Johnston SL (2005) Toll-like receptor 3 is induced by and mediates antiviral activity against rhinovirus infection of human bronchial epithelial cells. J Virol 79:12273–12279

    Article  PubMed  CAS  Google Scholar 

  84. Wesch D, Marx S, Kabelitz D (1997) Comparative analysis of α β and γδ T cell activation by Mycobacterium tuberculosis and isopentenyl pyrophosphate. Eur J Immunol 27:952–956

    Article  PubMed  CAS  Google Scholar 

  85. Sciammas R, Kodukula P, Tang Q, Hendricks RL, Bluestone JA (1997) T cell receptor-γ/δ cells protect mice from herpes simplex virus type 1-induced lethal encephalitis. J Exp Med 185:1969–1975

    Article  PubMed  CAS  Google Scholar 

  86. Sciammas R, Bluestone JA (1998) HSV-1 glycoprotein I-reactive TCR γδ cells directly recognize the peptide backbone in a conformationally dependent manner. J Immunol 161:5187–5192

    PubMed  CAS  Google Scholar 

  87. O’Riordan DP, Golden WC, Aucott SW (2006) Herpes simplex virus infections in preterm infants. Pediatrics 118:e1612–e1620

    Article  PubMed  Google Scholar 

  88. Yoshimura A, Lien E, Ingalls RR, Tuomanen E, Dziarski R, Golenbock D (1999) Cutting edge: recognition of Gram-positive bacterial cell wall components by the innate immune system occurs via Toll-like receptor 2. J Immunol 163:1–5

    PubMed  CAS  Google Scholar 

  89. Akashi-Takamura S, Miyake K (2008) TLR accessory molecules. Curr Opin Immunol 20:420–425

    Article  PubMed  CAS  Google Scholar 

  90. Ismaili J, Rennesson J, Aksoy E, Vekemans J, Vincart B, Amraoui Z, Van LF, Goldman M, Dubois PM (2002) Monophosphoryl lipid A activates both human dendritic cells and T cells. J Immunol 168:926–932

    PubMed  CAS  Google Scholar 

  91. Sasaki S, Hamajima K, Fukushima J, Ihata A, Ishii N, Gorai I, Hirahara F, Mohri H, Okuda K (1998) Comparison of intranasal and intramuscular immunization against human immunodeficiency virus type 1 with a DNA-monophosphoryl lipid A adjuvant vaccine. Infect Immun 66:823–826

    PubMed  CAS  Google Scholar 

  92. Makkouk A, Abdelnoor AM (2009) The potential use of Toll-like receptor (TLR) agonists and antagonists as prophylactic and/or therapeutic agents. Immunopharmacol Immunotoxicol 31:331–338

    Article  PubMed  CAS  Google Scholar 

  93. Shimura H, Nitahara A, Ito A, Tomiyama K, Ito M, Kawai K (2005) Up-regulation of cell surface Toll-like receptor 4-MD2 expression on dendritic epidermal T cells after the emigration from epidermis during cutaneous inflammation. J Dermatol Sci 37:101–110

    Article  PubMed  CAS  Google Scholar 

  94. Fang H, Welte T, Zheng X, Chang GJ, Holbrook MR, Soong L, Wang T (2010) γδ T cells promote the maturation of dendritic cells during West Nile virus infection. FEMS Immunol Med Microbiol 59:71–80

    Article  PubMed  CAS  Google Scholar 

  95. Pieper J, Methner U, Berndt A (2008) Heterogeneity of avian γδ T cells. Vet Immunol Immunopathol 124:241–252

    Article  PubMed  CAS  Google Scholar 

  96. Chalifour A, Jeannin P, Gauchat JF, Blaecke A, Malissard M, N’Guyen T, Thieblemont N, Delneste Y (2004) Direct bacterial protein PAMP recognition by human NK cells involves TLRs and triggers alpha-defensin production. Blood 104:1778–1783

    Article  PubMed  CAS  Google Scholar 

  97. Means TK, Hayashi F, Smith KD, Aderem A, Luster AD (2003) The Toll-like receptor 5 stimulus bacterial flagellin induces maturation and chemokine production in human dendritic cells. J Immunol 170:5165–5175

    PubMed  CAS  Google Scholar 

  98. Crellin NK, Garcia RV, Hadisfar O, Allan SE, Steiner TS, Levings MK (2005) Human CD4+ T cells express TLR5 and its ligand flagellin enhances the suppressive capacity and expression of FOXP3 in CD4+ CD25+ T regulatory cells. J Immunol 175:8051–8059

    PubMed  CAS  Google Scholar 

  99. Vijay-Kumar M, Sanders CJ, Taylor RT, Kumar A, Aitken JD, Sitaraman SV, Neish AS, Uematsu S, Akira S, Williams IR, Gewirtz AT (2007) Deletion of TLR5 results in spontaneous colitis in mice. J Clin Invest 117:3909–3921

    PubMed  CAS  Google Scholar 

  100. Gewirtz AT, Vijay-Kumar M, Brant SR, Duerr RH, Nicolae DL, Cho JH (2006) Dominant-negative TLR5 polymorphism reduces adaptive immune response to flagellin and negatively associates with Crohn’s disease. Am J Physiol Gastrointest Liver Physiol 290:G1157–G1163

    Article  PubMed  CAS  Google Scholar 

  101. Burdelya LG, Krivokrysenko VI, Tallant TC, Strom E, Gleiberman AS, Gupta D, Kurnasov OV, Fort FL, Osterman AL, Didonato JA, Feinstein E, Gudkov AV (2008) An agonist of Toll-like receptor 5 has radioprotective activity in mouse and primate models. Science 320:226–230

    Article  PubMed  CAS  Google Scholar 

  102. Dockrell DH, Kinghorn GR (2001) Imiquimod and resiquimod as novel immunomodulators. J Antimicrob Chemother 48:751–755

    Article  PubMed  CAS  Google Scholar 

  103. Rajagopal D, Paturel C, Morel Y, Uematsu S, Akira S, Diebold SS (2010) Plasmacytoid dendritic cell-derived type I interferon is crucial for the adjuvant activity of Toll-like receptor 7 agonists. Blood 115:1949–1957

    Article  PubMed  CAS  Google Scholar 

  104. Lee HK, Lund JM, Ramanathan B, Mizushima N, Iwasaki A (2007) Autophagy-dependent viral recognition by plasmacytoid dendritic cells. Science 315:1398–1401

    Article  PubMed  CAS  Google Scholar 

  105. Schon MP, Schon M (2008) TLR7 and TLR8 as targets in cancer therapy. Oncogene 27:190–199

    Article  PubMed  CAS  Google Scholar 

  106. Vollmer J, Krieg AM (2009) Immunotherapeutic applications of CpG oligodeoxynucleotide TLR9 agonists. Adv Drug Deliv Rev 61:195–204

    Article  PubMed  CAS  Google Scholar 

  107. Yarovinsky F, Zhang D, Andersen JF, Bannenberg GL, Serhan CN, Hayden MS, Hieny S, Sutterwala FS, Flavell RA, Ghosh S, Sher A (2005) TLR11 activation of dendritic cells by a protozoan profilin-like protein. Science 308:1626–1629

    Article  PubMed  CAS  Google Scholar 

  108. Zhang D, Zhang G, Hayden MS, Greenblatt MB, Bussey C, Flavell RA, Ghosh S (2004) A Toll-like receptor that prevents infection by uropathogenic bacteria. Science 303:1522–1526

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

D. Wesch and D. Kabelitz gratefully acknowledge the financial support within the Priority Program 1110 (Ka 502/8-1-3) and the SFB 415 (project A15) of the Deutsche Forschungsgemeinschaft. We also thank the Werner und Klara Kreitz Stiftung for their grant support.

Conflict-of-interest disclosure

The authors declare no competing financial interests.

Author information

Authors and Affiliations

  1. Institute of Immunology, Christian-Albrechts University Kiel, Arnold-Heller Strasse 3, Haus 17, 24105, Kiel, Germany

    Daniela Wesch, Christian Peters, Hans-Heinrich Oberg, Kathrin Pietschmann & Dieter Kabelitz

Authors
  1. Daniela Wesch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christian Peters
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hans-Heinrich Oberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kathrin Pietschmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dieter Kabelitz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daniela Wesch.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wesch, D., Peters, C., Oberg, HH. et al. Modulation of γδ T cell responses by TLR ligands. Cell. Mol. Life Sci. 68, 2357–2370 (2011). https://doi.org/10.1007/s00018-011-0699-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-011-0699-1

Keywords

Search

Navigation