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 FcRγ 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.

Th cells producing IL‐17 play a pro‐inflammatory role at mucosal surfaces. Treg at the same sites dampen inflammation and prevent immunopathology. Th cells producing IL‐17 (Th17) and Treg are thought to be distinct populations defined by expression of the transcription factors ROR‐γt and Foxp3, respectively. Here, we show that mouse CD25⁺Foxp3⁺ Treg can be converted into a hybrid T‐cell population characterized by the expression of Foxp3 and ROR‐γt and the production of IL‐17. Conversion was observed upon coculture with DC selectively activated via dectin‐1, a C‐type lectin receptor involved in fungal recognition, and depended on IL‐23 produced by DC. Within the Foxp3⁺ population, only Foxp3⁺ROR‐γt⁺ T cells but not Foxp3⁺ROR‐γt^‐–T cells become Foxp3⁺IL‐17⁺ T cells. These results indicate that some Foxp3⁺ T cells can produce IL‐17 while retaining Foxp3 expression and suggest that Treg could play an unexpected pro‐inflammatory role in some settings.