Syk- and Card9-dependent coupling of innate immunity to TH-17 responses.

LeibundGut-Landmann, S., O. Groß, M.J. Robinson, F. Osorio, E.C. Slack, S.V. Tsoni, E. Schweighoffer, V. Tybulewicz, G.D. Brown, J. Ruland, and Reis e Sousa C.
Nature Immunol, 8:630-638, 2007.

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 (T(H)-17 cells) in vitro, and a dectin-1 agonist acted as an adjuvant promoting the differentiation of T(H)-17 and T helper type 1 cells in vivo. Infection with Candida albicans induced CARD9-dependent T(H)-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 T(H)-17 responses to some pathogens.

URL: http://www.nature.com/ni/journal/v8/n6/abs/ni1460.html

Pub Med: http://www.ncbi.nlm.nih.gov/pubmed/17450144

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