Selective C-Rel activation via Malt1 controls anti-fungal T(H)-17 immunity by dectin-1 and dectin-2

TY - JOUR

T1 - Selective C-Rel activation via Malt1 controls anti-fungal T(H)-17 immunity by dectin-1 and dectin-2

AU - Gringhuis, S.I.

AU - Wevers, B.A.

AU - Kaptein, T.M.

AU - van Capel, T.M.

AU - Theelen, B.J.F.

AU - Boekhout, T.

AU - de Jong, E.C.

AU - Geijtenbeek, T.B.H.

N1 - Reporting year: 2011 Metis note: 3024268;

PY - 2011

Y1 - 2011

N2 - C-type lectins dectin-1 and dectin-2 on dendritic cells elicit protective immunity against fungal infections through induction of T(H)1 and T(H)-17 cellular responses. Fungal recognition by dectin-1 on human dendritic cells engages the CARD9-Bcl10-Malt1 module to activate NF-kappaB. Here we demonstrate that Malt1 recruitment is pivotal to T(H)-17 immunity by selective activation of NF-kappaB subunit c-Rel, which induces expression of T(H)-17-polarizing cytokines IL-1beta and IL-23p19. Malt1 inhibition abrogates c-Rel activation and T(H)-17 immunity to Candida species. We found that Malt1-mediated activation of c-Rel is similarly essential to induction of T(H)-17-polarizing cytokines by dectin-2. Whereas dectin-1 activates all NF-kappaB subunits, dectin-2 selectively activates c-Rel, signifying a specialized T(H)-17-enhancing function for dectin-2 in anti-fungal immunity by human dendritic cells. Thus, dectin-1 and dectin-2 control adaptive T(H)-17 immunity to fungi via Malt1-dependent activation of c-Rel. [KEYWORDS: Adaptive Immunity/immunology ,Candida/immunology ,Caspases/antagonists & inhibitors/genetics/*metabolism ,Cells, Cultured ,DNA-Binding Proteins/genetics/*metabolism ,Dendritic Cells/*immunology/metabolism ,Gene Expression Regulation ,Humans ,Interleukin-1beta/metabolism ,Interleukin-23 Subunit p19/metabolism ,Lectins, C-Type/genetics/*metabolism ,Membrane Proteins/genetics/*metabolism ,Neoplasm Proteins/antagonists & inhibitors/genetics/*metabolism ,Nerve Tissue Proteins/genetics/*met

AB - C-type lectins dectin-1 and dectin-2 on dendritic cells elicit protective immunity against fungal infections through induction of T(H)1 and T(H)-17 cellular responses. Fungal recognition by dectin-1 on human dendritic cells engages the CARD9-Bcl10-Malt1 module to activate NF-kappaB. Here we demonstrate that Malt1 recruitment is pivotal to T(H)-17 immunity by selective activation of NF-kappaB subunit c-Rel, which induces expression of T(H)-17-polarizing cytokines IL-1beta and IL-23p19. Malt1 inhibition abrogates c-Rel activation and T(H)-17 immunity to Candida species. We found that Malt1-mediated activation of c-Rel is similarly essential to induction of T(H)-17-polarizing cytokines by dectin-2. Whereas dectin-1 activates all NF-kappaB subunits, dectin-2 selectively activates c-Rel, signifying a specialized T(H)-17-enhancing function for dectin-2 in anti-fungal immunity by human dendritic cells. Thus, dectin-1 and dectin-2 control adaptive T(H)-17 immunity to fungi via Malt1-dependent activation of c-Rel. [KEYWORDS: Adaptive Immunity/immunology ,Candida/immunology ,Caspases/antagonists & inhibitors/genetics/*metabolism ,Cells, Cultured ,DNA-Binding Proteins/genetics/*metabolism ,Dendritic Cells/*immunology/metabolism ,Gene Expression Regulation ,Humans ,Interleukin-1beta/metabolism ,Interleukin-23 Subunit p19/metabolism ,Lectins, C-Type/genetics/*metabolism ,Membrane Proteins/genetics/*metabolism ,Neoplasm Proteins/antagonists & inhibitors/genetics/*metabolism ,Nerve Tissue Proteins/genetics/*met

U2 - 10.1371/journal.ppat.1001259

DO - 10.1371/journal.ppat.1001259

M3 - Article

SN - 1553-7366

VL - 7

SP - 1001259

JO - PLoS Pathogens

JF - PLoS Pathogens

IS - 1

ER -