Fungal recognition by Dectin-1 on dendritic cells induces IL-10 producing CD4+ T cells by GATA3 / C/EBP-β pathway (MPF4P.733)

Abstract

Abstract C. Albicans is known to dramatically transit its morphology between the yeast and hyphal form, depending on its environment. In order to show how these two types of C. Albicans may induce T cell responses, naïve T cells were stimulated with bone marrow-derived dendritic cells in the presence of either form of this organism. The cells stimulated with the hyphal form produced high amount of immunosuppressive IL-10, but not when stimulated with the yeast form. As C. Albicans expresses various innate receptor ligands, T cells were stimulated in presence of both Dectin-1- and/or TLR2-specific ligands. The T cells produced IL-10 when stimulated with Dectin-1 ligand alone, but not when stimulated with both Dectin-1 and TLR2 ligands. This suggests that the hyphal form predominantly express Dectin-1 ligands whereas the yeast form express both Dectin-1 and TLR2 ligands. In accompanying molecular studies, we found that Dectin-1 stimulation (but not Dectin-1 plus TLR2 stimulation) leads to IL-4 production and that Dectin-1-stimulated IL-4-, STAT6-, and GATA3-deficient CD4+ T cells produce greatly reduced amounts of IL-10. Furthermore, CCAAT/enhancer-binding protein beta (C/EBP-β) KO CD4+ T cells were also deficient in IL-10 production. Finally, we found that C/EBP-β interacts with GATA3 and influences its function. Thus, Dectin-1-induced IL-10 production stimulated by certain fungal forms is set in motion by a GATA3 / C/EBP-β mediated effect on IL-10 transcription.