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

TLDR

Innate immune cells use pattern recognition receptors to initiate responses, and studies of the fungal PRR Dectin‑1 have revealed a Syk‑CARD9 pathway essential for Th17 responses. Unlike Dectin‑1, Dectin‑2 couples to Syk indirectly through association with the FcRγ chain. Dectin‑2 signals through Syk‑CARD9 via FcRγ, activates dendritic cells, and is required for Candida‑specific IL‑17 production and Th1 responses, making it a key fungal PRR that regulates adaptive immunity.

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 FcRgamma 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.