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

• Published in: Immunity (Cambridge, Mass.) Vol. 32; no. 5; pp. 681 - 691
• Main Authors: Saijo, Shinobu, Ikeda, Satoshi, Yamabe, Keiko, Kakuta, Shigeru, Ishigame, Harumichi, Akitsu, Aoi, Fujikado, Noriyuki, Kusaka, Toshimasa, Kubo, Sachiko, Chung, Soo-hyun, Komatsu, Ryohei, Miura, Noriko, Adachi, Yoshiyuki, Ohno, Naohito, Shibuya, Kazutoshi, Yamamoto, Natsuo, Kawakami, Kazuyoshi, Yamasaki, Sho, Saito, Takashi, Akira, Shizuo, Iwakura, Yoichiro
• Format: Journal Article
• Language: English
• Published: Cambridge Elsevier Limited 28.05.2010
• Subjects: Autoimmune diseases; Bacterial infections; Candida albicans; Carbohydrates; Defense mechanisms; Fungal infections; Grants; Immune system; Phosphorylation; Science; Technological change
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2010.05.001

Dectin-2 (gene symbolClec4n) 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 generatedClec4n-/-mice and showed that this molecule is important for host defense againstCandida 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 ofC. albicansinduced 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 againstC. albicansby inducing Th17 cell differentiation.