title: c-Rel promotes type 1 and type 17 immune responses during Leishmania major infection.
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-γ 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 naïve 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.
authors.affiliation: Institute for Medical Microbiology and Hygiene, University of Marburg, Marburg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Reinhard
authors.forename: Magdalena
authors.initials: M
authors.lastname: Huber
authors.forename: Corinna
authors.initials: C
authors.lastname: Wostl
authors.forename: Anne
authors.initials: A
authors.lastname: Hellhund
authors.forename: Anne
authors.initials: A
authors.lastname: Toboldt
authors.forename: Elfadil
authors.initials: E
authors.lastname: Abass
authors.forename: Bärbel
authors.initials: B
authors.lastname: Casper
authors.forename: Thorsten
authors.initials: T
authors.lastname: Joeris
authors.forename: Christian
authors.initials: C
authors.lastname: Herr
authors.forename: Robert
authors.initials: R
authors.lastname: Bals
authors.forename: Ulrich
authors.initials: U
authors.lastname: Steinhoff
authors.forename: Michael
authors.initials: M
authors.lastname: Lohoff
authors.forename: Alexander
authors.initials: A
authors.lastname: Visekruna
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D018398:Homeodomain Proteins / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000172:deficiency / Q000235:genetics; D020381:Interleukin-17 / Q000096:biosynthesis; D053759:Interleukin-23 / Q000235:genetics; D018320:Leishmania major / Q000276:immunology* / Q000502:physiology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020569:Proto-Oncogene Proteins c-rel / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D018398:Homeodomain Proteins; D020381:Interleukin-17; D053759:Interleukin-23; D020569:Proto-Oncogene Proteins c-rel; C064658:RAG-1 protein; D018664:Interleukin-12; D007371:Interferon-gamma