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

S.I. Gringhuis, B.A. Wevers, T.M. Kaptein, T.M. van Capel, B.J.F. Theelen, T. Boekhout, E.C. de Jong, T.B.H. Geijtenbeek

    Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgaveArtikelWetenschappelijkpeer review

    139 Citaten (Scopus)

    Samenvatting

    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
    Originele taal-2Engels
    Pagina's (van-tot)1001259
    TijdschriftPLoS Pathogens
    Volume7
    Nummer van het tijdschrift1
    DOI's
    StatusGepubliceerd - 2011

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