Selective c-Rel activation via Malt1 controls anti-fungal TH-17 immunity by dectin-1 and dectin-2

C-type lectins dectin-1 and dectin-2 on dendritic cells elicit protective immunity against fungal infections through induction of th1 and th-17 cellular responses. fungal recognition by dectin-1 on human dendritic cells engages the card9-bcl10-malt1 module to activate nf-κb. here we demonstrate that malt1 recruitment is pivotal to th-17 immunity by selective activation of nf-κb subunit c-rel,which induces expression of th-17-polarizing cytokines il-1β and il-23p19. malt1 inhibition abrogates c-rel activation and th-17 immunity to candida species. we found that malt1-mediated activation of c-rel is similarly essential to induction of th-17-polarizing cytokines by dectin-2. whereas dectin-1 activates all nf-κb subunits,dectin-2 selectively activates c-rel,signifying a specialized th-17-enhancing function for dectin-2 in anti-fungal immunity by human dendritic cells. thus,dectin-1 and dectin-2 control adaptive th-17 immunity to fungi via malt1-dependent activation of c-rel. © 2011 gringhuis et al.