nach oben

Medical Microbiology and Immunology

Erschienen in:

01.03.2008 | Original Investigation

TNF controls the infiltration of dendritic cells into the site of Leishmania major infection

verfasst von: Uwe Ritter, Anja Lechner, Katja Scharl, Ziba Kiafard, Jörg Zwirner, Heinrich Körner

Erschienen in: Medical Microbiology and Immunology | Ausgabe 1/2008

Einloggen, um Zugang zu erhalten

Abstract

TNF-negative C57BL/6 (B6.TNF^−/−) mice are highly susceptible to Leishmania (L.) major infection and succumb rapidly to fatal leishmaniasis. A T helper type 1 (Th1) cell-mediated immune response is central for protective anti-leishmanial immunity. Therefore, the observed susceptibility of B6.TNF^−/− mice to L. major parasites could be caused by a deficiency in mounting a Th1 response. Analysis of infected footpads revealed, that B6.TNF^−/− mice exhibited a substantially diminished formation of DCs at the site of infection. Furthermore, Th1 cytokines such as IFN-γ were reduced in footpads of infected B6.TNF^−/− mice. Cutaneous reconstitution of B6.TNF^−/− mice with either bone marrow derived DCs (BM-DCs) or recombinant TNF simultaneous to infection resulted in an increased expression of cytokines such as IFN-γ and in an enhanced presence of Leishmania-antigen in skin draining lymph nodes. In addition, the individual time of survival was doubled. In conclusion we demonstrate that the expression of dermal TNF is necessary to provide an environment that initiates a local inflammatory response, but is not sufficient to induce protective immunity.

Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B, Palucka K (2000) Immunobiology of dendritic cells. Annu Rev Immunol 18:767–811PubMedCrossRef

Kelsall BL, Biron CA, Sharma O, Kaye PM (2002) Dendritic cells at the host-pathogen interface. Nat Immunol 3:699–702PubMedCrossRef

Serbina NV, Salazar-Mather TP, Biron CA, Kuziel WA, Pamer EG (2003) TNF/iNOS-producing dendritic cells mediate innate immune defense against bacterial infection. Immunity 19:59–70PubMedCrossRef

Martin-Fontecha A, Sebastiani S, Hopken UE, Uguccioni M, Lipp M, Lanzavecchia A, Sallusto F (2003) Regulation of dendritic cell migration to the draining lymph node: impact on T lymphocyte traffic and priming. J Exp Med 198:615–621PubMedCrossRef

Ritter U, Mattner J, Rocha JS, Bogdan C, Korner H (2004) The control of Leishmania (Leishmania) major by TNF in vivo is dependent on the parasite strain. Microbes Infect 6:559–565PubMedCrossRef

Ritter U, Meissner A, Ott J, Korner H (2003) Analysis of the maturation process of dendritic cells deficient for TNF and lymphotoxin-alpha reveals an essential role for TNF. J Leukoc Biol 74:216–222PubMedCrossRef

Ohl L, Mohaupt M, Czeloth N, Hintzen G, Kiafard Z, Zwirner J, Blankenstein T, Henning G, Forster R (2004) CCR7 governs skin dendritic cell migration under inflammatory and steady-state conditions. Immunity 21:279–288PubMedCrossRef

Sacks D, Noben-Trauth N (2002) The immunology of susceptibility and resistance to Leishmania major in mice. Nat Rev Immunol 2:845–858PubMedCrossRef

Solbach W, Laskay T (2000) The host response to Leishmania infection. Adv Immunol 74:275–317PubMedCrossRef

10.

Diefenbach A, Schindler H, Donhauser N, Lorenz E, Laskay T, MacMicking J, Röllinghoff M, Gresser I, Bogdan C (1998) Type 1 interferon (IFN-α/β) and type 2 nitric oxide synthase regulate the innate immune response to a protozoan parasite. Immunity 8:77–87PubMedCrossRef

11.

Scharton-Kersten T, Afonso LC, Wysocka M, Trinchieri G, Scott P (1995) IL-12 is required for natural killer cell activation and subsequent T helper 1 cell development in experimental leishmaniasis. J Immunol 154:5320–5330PubMed

12.

Malherbe L, Filippi C, Julia V, Foucras G, Moro M, Appel H, Wucherpfennig K, Guery JC, Glaichenhaus N (2000) Selective activation and expansion of high-affinity CD4+ T cells in resistant mice upon infection with Leishmania major. Immunity 13:771–782PubMedCrossRef

13.

Himmelrich H, Launois P, Maillard I, Biedermann T, Tacchini-Cottier F, Locksley RM, Rocken M, Louis JA (2000) In BALB/c mice, IL-4 production during the initial phase of infection with Leishmania major is necessary and sufficient to instruct Th2 cell development resulting in progressive disease. J Immunol 164:4819–4825PubMed

14.

Wilhelm P, Ritter U, Labbow S, Donhauser N, Rollinghoff M, Bogdan C, Korner H (2001) Rapidly fatal leishmaniasis in resistant C57BL/6 mice lacking TNF. J Immunol 166:4012–4019PubMed

15.

Leon B, Lopez-Bravo M, Ardavin C (2007) Monocyte-derived dendritic cells formed at the infection site control the induction of protective T Helper 1 responses against Leishmania. Immunity 26:519–531PubMedCrossRef

16.

Körner H, Cook M, Riminton DS, Lemckert FA, Hoek R, Ledermann B, Köntgen F, Fazekas de St Groth B, Sedgwick JD (1997) Distinct roles for lymphotoxin-α and tumour necrosis factor in lymphoid tissue organogenesis and spatial organisation defined in gene targeted C57BL/6 Mice. Eur J Immunol 27:2600–2609PubMedCrossRef

17.

Wilhelm P, Riminton DS, Ritter U, Lemckert FA, Scheidig C, Hoek R, Sedgwick JD, Korner H (2002) Membrane lymphotoxin contributes to anti-leishmanial immunity by controlling structural integrity of lymphoid organs. Eur J Immunol 32:1993–2003PubMedCrossRef

18.

Solbach W, Forberg K, Kammerer E, Bogdan C, Röllinghoff M (1986) Suppressive effect of cyclosporin A on the development of Leishmania tropica-induced lesions in genetically susceptible BALB/c mice. J Immunol 137:702–711PubMed

19.

Wilhelm P, Ritter U, Labbow S, Donhauser N, Röllinghoff M, Bogdan C, Körner H (2001) Rapidly fatal Leishmaniasis in resistant C57BL/6 mice lacking TNF. J Immunol 166:4012–4019PubMed

20.

Ritter U, Mattner J, Rocha JS, Bogdan C, Körner H (2004) The control of Leishmania (Leishmania) major by TNF in vivo is dependent on the parasite strain. Microbes Infect 6:559–565PubMedCrossRef

21.

Higuchi R, Fockler C, Dollinger G, Watson R (1993) Kinetic PCR analysis: real-time monitoring of DNA amplification reactions. Biotechnology (N Y) 11:1026–1030CrossRef

22.

Ponchel F, Toomes C, Bransfield K, Leong FT, Douglas SH, Field SL, Bell SM, Combaret V, Puisieux A, Mighell AJ, Robinson PA, Inglehearn CF, Isaacs JD, Markham AF (2003) Real-time PCR based on SYBR-Green I fluorescence: an alternative to the TaqMan assay for a relative quantification of gene rearrangements, gene amplifications and micro gene deletions. BMC Biotechnol 3:18PubMedCrossRef

23.

Lutz MB, Kukutsch N, Ogilvie AL, Rossner S, Koch F, Romani N, Schuler G (1999) An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow. J Immunol Methods 223:77–92PubMedCrossRef

24.

Anderson CF, Oukka M, Kuchroo VJ, Sacks D (2007) CD4(+)CD25(-)Foxp3(-) Th1 cells are the source of IL-10-mediated immune suppression in chronic cutaneous leishmaniasis. J Exp Med 204:285–297PubMedCrossRef

25.

Jankovic D, Kullberg MC, Feng CG, Goldszmid RS, Collazo CM, Wilson M, Wynn TA, Kamanaka M, Flavell RA, Sher A (2007) Conventional T-bet(+)Foxp3(-) Th1 cells are the major source of host-protective regulatory IL-10 during intracellular protozoan infection. J Exp Med 204:273–283PubMedCrossRef

26.

Misslitz AC, Bonhagen K, Harbecke D, Lippuner C, Kamradt T, Aebischer T (2004) Two waves of antigen-containing dendritic cells in vivo in experimental Leishmania major infection. Eur J Immunol 34:715–725PubMedCrossRef

27.

Bazzoni F, Beutler B (1996) The tumour necrosis factor ligand and receptor families. N Engl J Med 334:1717–1725PubMedCrossRef

28.

Neumann B, Machleidt T, Lifka A, Pfeffer K, Vestweber D, Mak TW, Holzmann B, Krönke M (1996) Crucial Role of 55-kilodalton TNF receptor in TNF-induced adhesion molecule expression and leukocyte organ infiltration. J Immunol 156:1587–1593PubMed

29.

Ngo VN, Körner H, Gunn MD, Schmidt KN, Riminton DS, Cooper MD, Browning JL, Sedgwick JD, Cyster JG (1999) Lymphotoxin alpha/beta and tumor necrosis factor are required for stromal cell expression of homing chemokines in B and T cell areas of the spleen. J Exp Med 189:403–412PubMedCrossRef

30.

Janatpour MJ, Hudak S, Sathe M, Sedgwick JD, McEvoy LM (2001) Tumor necrosis factor-dependent segmental control of MIG expression by high endothelial venules in inflamed lymph nodes regulates monocyte recruitment. J Exp Med 194:1375–1384PubMedCrossRef

31.

von Stebut E, Metz M, Milon G, Knop J, Maurer M (2003) Early macrophage influx to sites of cutaneous granuloma formation is dependent on MIP-1alpha /beta released from neutrophils recruited by mast cell-derived TNFalpha. Blood 101:210–215CrossRef

32.

Steinman RM, Pack M, Inaba K (1997) Dendritic cells in the T-cell areas of lymphoid organs. Immunol Rev 156:25–37PubMedCrossRef

33.

Ritter U, Korner H (2002) Divergent expression of inflammatory dermal chemokines in cutaneous leishmaniasis. Parasite Immunol 24:295–301PubMedCrossRef

34.

Ritter U, and Osterloh A (2006) A new view on cutaneous dendritic cell subsets in experimental leishmaniasis. Med Microbiol Immunol (Berl)

Titel: TNF controls the infiltration of dendritic cells into the site of Leishmania major infection
verfasst von: Uwe Ritter
Anja Lechner
Katja Scharl
Ziba Kiafard
Jörg Zwirner
Heinrich Körner
Publikationsdatum: 01.03.2008
Verlag: Springer-Verlag
Erschienen in: Medical Microbiology and Immunology / Ausgabe 1/2008
Print ISSN: 0300-8584
Elektronische ISSN: 1432-1831
DOI: https://doi.org/10.1007/s00430-007-0056-z

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Reizdarmsyndrom: Diäten wirksamer als Medikamente

29.04.2024 Reizdarmsyndrom Nachrichten

Bei Reizdarmsyndrom scheinen Diäten, wie etwa die FODMAP-arme oder die kohlenhydratreduzierte Ernährung, effektiver als eine medikamentöse Therapie zu sein. Das hat eine Studie aus Schweden ergeben, die die drei Therapieoptionen im direkten Vergleich analysierte.

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

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.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2008

Heat shock proteins: linking danger and pathogen recognition

Inhibition of hemagglutination activity of influenza A viruses by SP-A1 and SP-A2 variants expressed in CHO cells

Multicenter study of a new fully automated HBsAg screening assay with enhanced sensitivity for the detection of HBV mutants

LPS inhalation challenge: a new tool to characterize the inflammatory response in humans

Fetal calf serum inhibits virus genome expression in Madin-Darby canine kidney cells persistently infected with influenza A virus