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

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


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.

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Título según WOS: ID WOS:000246703300017 Not found in local WOS DB
Título de la Revista: NATURE IMMUNOLOGY
Volumen: 8
Número: 6
Fecha de publicación: 2007
Página de inicio: 630
Página final: 638


Notas: ISI