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

被引:136
作者
Gringhuis, Sonja I. [1 ,2 ]
Wevers, Brigitte A. [1 ,2 ]
Kaptein, Tanja M. [1 ,2 ]
van Capel, Toni M. M. [3 ]
Theelen, Bart [4 ]
Boekhout, Teun [4 ]
de Jong, Esther C. [3 ]
Geijtenbeek, Teunis B. H. [1 ,2 ]
机构
[1] Univ Amsterdam, Acad Med Ctr, Ctr Infect & Immun Amsterdam, NL-1105 AZ Amsterdam, Netherlands
[2] Univ Amsterdam, Acad Med Ctr, Ctr Expt & Mol Med, NL-1105 AZ Amsterdam, Netherlands
[3] Univ Amsterdam, Acad Med Ctr, Dept Cell Biol & Histol, NL-1105 AZ Amsterdam, Netherlands
[4] CBS KNAW Fungal Biodivers Ctr, Utrecht, Netherlands
关键词
PATTERN-RECOGNITION RECEPTOR; INNATE IMMUNITY; HOST-DEFENSE; CELL-WALL; PATHOGENIC FUNGUS; CANDIDA-ALBICANS; INDUCTION; LECTIN; STIMULATION; CYTOKINES;
D O I
10.1371/journal.ppat.1001259
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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-kappa B. Here we demonstrate that Malt1 recruitment is pivotal to T-H-17 immunity by selective activation of NF-kappa B subunit c-Rel, which induces expression of T-H-17-polarizing cytokines IL-1 beta 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-kappa B 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.
引用
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页数:11
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