c-Rel promotes type 1 and type 17 immune responses during Leishmania major infection

Katharina Reinhard, Magdalena Huber, Corinna Wostl, Anne Hellhund, Anne Toboldt, Elfadil Abass, Baerbel Casper, Thorsten Joeris, Christian Herr, Robert Bals, Ulrich Steinhoff, Michael Lohoff, Alexander Visekruna

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Recent studies demonstrated the crucial role of c-Rel in directing Treg lineage commitment and its involvement in T helper 1 (Th1) cell-mediated autoimmune inflammation. We thus wondered whether these opposite functions of c-Rel influence the course of antiparasitic immune responses against Leishmania major, an accepted model for the impact of T-cell subsets on disease outcome. Here we show that c-Rel-deficient (rel(-/-)) mice infected with L. major displayed dramatically exacerbated leishmaniasis and enhanced parasite burdens. In contrast to WT mice, IFN-gamma and IL-17 production in response to L. major antigens was severely impaired in rel(-/-) mice. Reconstitution of Rag1(-/-) T-cell deficient mice with rel(-/-) CD4(+) T cells followed by L. major infection demonstrated that c-Rel-deficient T cells mount normal Th1 responses and are able to contain the infection. Similarly, Th1 differentiation of naive CD4(+) cells in vitro was normal. Notably, a selective defect in IL-12 and IL-23 production was observed in rel(-/-) DCs compared with their WT counterparts. In conclusion, our data suggest that the expression of c-Rel in myeloid cells is essential for clearance of L. major and that this c-Rel-mediated effect is dominant over the lack of Tregs.
Original languageEnglish
JournalEuropean Journal of Immunology
Volume41
Issue number5
Pages (from-to)1388-1398
Number of pages11
ISSN0014-2980
DOIs
Publication statusPublished - 2011
Externally publishedYes

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