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. © 2007 Springer-Verlag.

Item Type:	Refereed Article
Research Division:	Biomedical and Clinical Sciences
Research Group:	Immunology
Research Field:	Immunology not elsewhere classified
Objective Division:	Health
Objective Group:	Clinical health
Objective Field:	Clinical health not elsewhere classified
UTAS Author:	Korner, H (Professor Heinrich Korner)
ID Code:	72532
Year Published:	2008
Web of Science® Times Cited:	11
Deposited By:	Research Division
Deposited On:	2011-08-29
Last Modified:	2011-08-29
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