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The Journal of Experimental Medicine

Year: 2009  |  Volume: 206  |  Issue: 9  |  Page No.: 2037 - 2051

Dectin-2 is a Syk-coupled pattern recognition receptor crucial for Th17 responses to fungal infection

M. J Robinson, F Osorio, M Rosas, R. P Freitas, E Schweighoffer, O Gross, J. S Verbeek, J Ruland, V Tybulewicz, G. D Brown, L. F Moita, P. R Taylor and C. Reis e Sousa

Abstract

Innate immune cells detect pathogens via pattern recognition receptors (PRRs), which signal for initiation of immune responses to infection. Studies with Dectin-1, a PRR for fungi, have defined a novel innate signaling pathway involving Syk kinase and the adaptor CARD9, which is critical for inducing Th17 responses to fungal infection. We show that another C-type lectin, Dectin-2, also signals via Syk and CARD9, and contributes to dendritic cell (DC) activation by fungal particles. Unlike Dectin-1, Dectin-2 couples to Syk indirectly, through association with the FcR chain. In a model of Candida albicans infection, blockade of Dectin-2 did not affect innate immune resistance but abrogated Candida-specific T cell production of IL-17 and, in combination with the absence of Dectin-1, decreased Th1 responses to the organism. Thus, Dectin-2 constitutes a major fungal PRR that can couple to the Syk–CARD9 innate signaling pathway to activate DCs and regulate adaptive immune responses to fungal infection.

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