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

被引：622

作者：

Saijo, Shinobu ^{[1
]}

Ikeda, Satoshi ^{[1
]}

Yamabe, Keiko ^{[1
]}

Kakuta, Shigeru ^{[1
]}

Ishigame, Harumichi ^{[1
]}

Akitsu, Aoi ^{[1
]}

Fujikado, Noriyuki ^{[1
]}

Kusaka, Toshimasa ^{[1
]}

Kubo, Sachiko ^{[1
]}

Chung, Soo-hyun ^{[1
]}

Komatsu, Ryohei ^{[1
]}

Miura, Noriko ^{[2
]}

Adachi, Yoshiyuki ^{[2
]}

Ohno, Naohito ^{[2
]}

Shibuya, Kazutoshi ^{[3
]}

Yamamoto, Natsuo ^{[4
,5
]}

Kawakami, Kazuyoshi ^{[6
]}

Yamasaki, Sho ^{[7
]}

Saito, Takashi ^{[7
,8
]}

Akira, Shizuo ^{[8
]}

Iwakura, Yoichiro ^{[1
,9
]}

机构：

[1] Univ Tokyo, Inst Med Sci, Ctr Expt Med & Syst Biol, Minato Ku, Tokyo 1088639, Japan

[2] Tokyo Univ Pharm & Life Sci, Sch Pharm, Lab Immunopharmacol Microbial Prod, Tokyo 1920392, Japan

[3] Toho Univ, Fac Med, Sch Med, Dept Surg Pathol,Ota Ku, Tokyo 1438541, Japan

[4] Tohoku Univ, Grad Sch Med, Dept Infect Control, Aoba Ku, Sendai, Miyagi 9808575, Japan

[5] Tohoku Univ, Grad Sch Med, Diagnost Lab, Aoba Ku, Sendai, Miyagi 9808575, Japan

[6] Tohoku Univ, Sch Hlth Sci, Dept Med Technol, Aoba Ku, Sendai, Miyagi 9808575, Japan

[7] RIKEN Res Ctr Allergy & Immunol, Lab Cell Signaling, Yokohama, Kanagawa 2300045, Japan

[8] Osaka Univ, WPI Immunol Frontier Res Ctr, Suita, Osaka 5650871, Japan

[9] Japan Sci & Technol Agcy, CREST, Kawaguchi, Saitama 3320012, Japan

来源：

IMMUNITY | 2010年 / 32卷 / 05期

关键词：

T-HELPER-CELLS; RECEPTOR; RESPONSES; INNATE; IL-17; IMMUNITY; IL-23; INTERLEUKIN-17A; REQUIREMENT; ASSOCIATION;

D O I：

10.1016/j.immuni.2010.05.001

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 FcR gamma chain and Syk-CARD9-NF-kappa B-dependent signaling pathway without involvement of MAP kinases. The yeast form of C. albicans induced interleukin-1 beta (IL-1 beta) 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.

引用

页码：681 / 691

页数：11

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