Dectin-2 Recognition of α-Mannans and Induction of Th17 Cell Differentiation Is Essential for Host Defense against Candida albicans

Dectin-2 (gene symbol Clec4n) is a C-type lectin expressed by dendritic cells (DCs) and macrophages. However, its functional roles and signaling mechanisms remain to be elucidated. Here, we generated Clec4n −/− mice and showed that this molecule is important for host defense against Candida albicans ( C. albicans). Clec4n −/− DCs had virtually no fungal α-mannan-induced cytokine production. Dectin-2 signaling induced cytokines through an FcRγ chain and Syk-CARD9-NF-κB-dependent signaling pathway without involvement of MAP kinases. The yeast form of C. albicans induced interleukin-1β (IL-1β) and IL-23 secretion in a Dectin-2-dependent manner. In contrast, cytokine production induced by the hyphal form was only partially dependent on this lectin. Both yeast and hyphae induced Th17 cell differentiation, in which Dectin-2, but not Dectin-1, was mainly involved. Because IL-17A-deficient mice were highly susceptible to systemic candida infection, this study suggests that Dectin-2 is important in host defense against C. albicans by inducing Th17 cell differentiation. ► Dectin-2 is a C-type lectin expressed by dendritic cells and recognizes α-mannans ► Dectin-2 transduces signals through an FcRγ and CARD9-NF-κB-dependent pathway ► Dectin-2 signaling promotes Th17 cell differentiation by inducing IL-1β and IL-23 ► Dectin-2 is important for the defense against Candida albicans by inducing Th17 cells