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

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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.

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Abbreviations

B6.WT:

C57BL/6

B6.TNF−/− :

C57BL/6-TNF−/−

LN:

Lymph node

L:

Leishmania

DC(s):

Dendritic cell(s)

LC(s):

Langerhans cell(s)

BM-DC:

Bone marrow (BM)-derived DC

SLC/CCL21:

Secondary lymphoid-tissue chemokine, or CCL21

ELC/CCL19:

Epstein-Barr virus-induced molecule 1 ligand chemokine, or CCL19

HEVs:

High endothelial venules; s.c., subcutaneously

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Acknowledgements

This work was supported by grants of the James Cook University (MRG and CRIG to HK), and by the Federal Ministry of Education and Research (BMBF) and the Interdisciplinary Center for Clinical Research (IZKF) at the University Hospital of the University of Erlangen-Nürnberg, Germany (HK, IZKF Nachwuchsgruppe 1).

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Authors and Affiliations

  1. Nachwuchsgruppe 1 des Interdisziplinären Zentrums für Klinische Forschung der, Universität Erlangen-Nürnberg, Erlangen, Germany

    Uwe Ritter & Katja Scharl

  2. Bernhard-Nocht-Institut für Tropenmedizin, Bernhard-Nocht-Strasse, Hamburg, Germany

    Uwe Ritter

  3. Institute for Immunology, University of Regensburg, Franz-Josef-Strauss Allee 11, 93053, Regensburg, Germany

    Uwe Ritter & Anja Lechner

  4. Abteilung für Immunologie, Georg-Augustus-Universität, Göttingen, Germany

    Ziba Kiafard & Jörg Zwirner

  5. Comparative Genomics Centre, School of Veterinary and Biomedical Science/School of Pharmacy and Molecular Sciences, James Cook University, Molecular Sciences Bld. 21, Townsville, QLD, 4811, Australia

    Heinrich Körner

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  1. Uwe Ritter
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  2. Anja Lechner
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Correspondence to Uwe Ritter or Heinrich Körner.

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Ritter, U., Lechner, A., Scharl, K. et al. TNF controls the infiltration of dendritic cells into the site of Leishmania major infection. Med Microbiol Immunol 197, 29–37 (2008). https://doi.org/10.1007/s00430-007-0056-z

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