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

Shinobu Saijo, Satoshi Ikeda, Keiko Yamabe, Shigeru Kakuta, Harumichi Ishigame, Aoi Akitsu, Noriyuki Fujikado, Toshimasa Kusaka, Sachiko Kubo, Soo hyun Chung, Ryohei Komatsu, Noriko Miura, Yoshiyuki Adachi, Naohito Ohno, Kazutoshi Shibuya, Natsuo Yamamoto, Kazuyoshi Kawakami, Sho Yamasaki, Takashi Saito, Shizuo AkiraYoichiro Iwakura

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449 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)681-691
Number of pages11
JournalImmunity
Volume32
Issue number5
DOIs
Publication statusPublished - May 2010

Keywords

  • Cellimmuno
  • Molimmuno
  • Signaling

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    Saijo, S., Ikeda, S., Yamabe, K., Kakuta, S., Ishigame, H., Akitsu, A., Fujikado, N., Kusaka, T., Kubo, S., Chung, S. H., Komatsu, R., Miura, N., Adachi, Y., Ohno, N., Shibuya, K., Yamamoto, N., Kawakami, K., Yamasaki, S., Saito, T., ... Iwakura, Y. (2010). Dectin-2 recognition of α-mannans and induction of Th17 cell differentiation is essential for host defense against candida albicans. Immunity, 32(5), 681-691. https://doi.org/10.1016/j.immuni.2010.05.001