[HTML][HTML] Selective C-Rel Activation via Malt1 Controls Anti-Fungal TH-17 Immunity by Dectin-1 and Dectin-2

SI Gringhuis, BA Wevers, TM Kaptein… - PLoS …, 2011 - journals.plos.org
SI Gringhuis, BA Wevers, TM Kaptein, TMM van Capel, B Theelen, T Boekhout, EC de Jong
PLoS pathogens, 2011journals.plos.org
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 …
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.
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