title: Dectin-2 recognition of alpha-mannans and induction of Th17 cell differentiation is essential for host defense against Candida albicans.
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 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.
authors.affiliation: Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku Tokyo 108-8639, Japan.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Saijo
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ikeda
authors.forename: Keiko
authors.initials: K
authors.lastname: Yamabe
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kakuta
authors.forename: Harumichi
authors.initials: H
authors.lastname: Ishigame
authors.forename: Aoi
authors.initials: A
authors.lastname: Akitsu
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Fujikado
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Kusaka
authors.forename: Sachiko
authors.initials: S
authors.lastname: Kubo
authors.forename: Soo-hyun
authors.initials: SH
authors.lastname: Chung
authors.forename: Ryohei
authors.initials: R
authors.lastname: Komatsu
authors.forename: Noriko
authors.initials: N
authors.lastname: Miura
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Adachi
authors.forename: Naohito
authors.initials: N
authors.lastname: Ohno
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Shibuya
authors.forename: Natsuo
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kawakami
authors.forename: Sho
authors.initials: S
authors.lastname: Yamasaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Saito
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D007118:Immunoassay; D020381:Interleukin-17 / Q000378:metabolism*; D053583:Interleukin-1beta / Q000276:immunology; D053759:Interleukin-23 / Q000276:immunology; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology*; D008297:Male; D008351:Mannans / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology
chemical_list: D020381:Interleukin-17; D053583:Interleukin-1beta; D053759:Interleukin-23; D037181:Lectins, C-Type; D008351:Mannans; C445340:dectin-2, mouse