TNF controls the infiltration of dendritic cells into the site of Leishmania major infection
Copyright policy )TNF controls the infiltration of dendritic cells into the site of Leishmania major infection
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-gamma 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-gamma 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.
- Leibniz Association Germany
- Bernhard Nocht Institute for Tropical Medicine Germany
- Institut für Immunologie Germany
- University of Erlangen-Nuremberg Germany
- University of Göttingen Germany
Inflammation, Immunity, Cellular, Chemokine CCL21, Foot, 610, Antibodies, Monoclonal, Leishmaniasis, Cutaneous, Dendritic Cells, Flow Cytometry, CD11c Antigen, Mice, Inbred C57BL, Interferon-gamma, Mice, Microscopy, Fluorescence, Cell Movement, Leukocytes, Animals, Leukocyte Common Antigens, Lymph Nodes, Leishmania major, Skin
Inflammation, Immunity, Cellular, Chemokine CCL21, Foot, 610, Antibodies, Monoclonal, Leishmaniasis, Cutaneous, Dendritic Cells, Flow Cytometry, CD11c Antigen, Mice, Inbred C57BL, Interferon-gamma, Mice, Microscopy, Fluorescence, Cell Movement, Leukocytes, Animals, Leukocyte Common Antigens, Lymph Nodes, Leishmania major, Skin
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