Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17

被引:930
作者
LeibundGut-Landmann, Salome
Gross, Olaf
Robinson, Matthew J.
Osorio, Fabiola
Slack, Emma C.
Tsoni, S. Vicky
Schweighoffer, Edina
Tybulewicz, Victor
Brown, Gordon D.
Ruland, Juergen
Sousa, Caetano Reis e [1 ]
机构
[1] London Res Inst, Canc Res UK, Lincolns Inn Fields Labs, Immunobiol Lab, London WC2A 3PX, England
[2] Tech Univ Munich, Klinikum Rechts Isar, Med Klin 3, D-81675 Munich, Germany
[3] Univ Cape Town, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa
[4] Natl Inst Med Res, London NW7 1AA, England
基金
英国医学研究理事会; 英国惠康基金; 瑞士国家科学基金会;
关键词
D O I
10.1038/ni1460
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The C-type lectin dectin-1 binds to yeast and signals through the kinase Syk and the adaptor CARD9 to induce production of interleukin 10 (IL-10) and IL-2 in dendritic cells (DCs). However, whether this pathway promotes full DC activation remains unclear. Here we show that dectin-1-Syk-CARD9 signaling induced DC maturation and the secretion of proinflammatory cytokines, including IL-6, tumor necrosis factor and IL-23, but little IL-12. Dectin-1-activated DCs 'instructed' the differentiation of CD4+ IL-17-producing effector T cells (TH-17 cells) in vitro, and a dectin-1 agonist acted as an adjuvant promoting the differentiation of TH-17 and T helper type 1 cells in vivo. Infection with Candida albicans induced CARD9-dependent TH-17 responses to the organism. Our data indicate that signaling through Syk and CARD9 can couple innate to adaptive immunity independently of Toll-like receptor signals and that CARD9 is required for the development of TH-17 responses to some pathogens.
引用
收藏
页码:630 / 638
页数:9
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