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Dectin-2 recognition of α-mannans and induction of Th17 cell differentiation is essential for host defense against Candida albicans.

Immunity doi:10.1016/j.9mmuni.2010.05.001
Shinobu Saijo1, Satoshi Ikeda1, Shigeru Kakuta1, Keiko Yamabe1, Harumichi Ishigame1, Noriyuki Fujikado1, Toshimasa Kusaka1, Sachiko Kubo1, Soohun Chung1, Ryohei Komatsu1, Noriko Miura2, Yoshiyuki Adachi2, Nohito Ohno2, Natsuo Yamamoto3, Kazuyoshi Kawakami4, Sho Yamasaki5*, Takashi Saito5,6, Shizuo Akira7 and Yoichiro Iwakura1,8

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 alpha-mannan-induced cytokine production. Dectin-2 signaling induced cytokines through an FcRgamma chain and Syk-CARD9-NF-kappaB-dependent signaling pathway without involvement of MAP kinases. The yeast form of C. albicans induced interleukin-1beta (IL-1beta) 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.