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 Akira; Yoichiro Iwakura

doi:10.1016/j.immuni.2010.05.001

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

MED - Health Sciences

Research output: Contribution to journal › Article › peer-review

556 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 language	English
Pages (from-to)	681-691
Number of pages	11
Journal	Immunity
Volume	32
Issue number	5
DOIs	https://doi.org/10.1016/j.immuni.2010.05.001
Publication status	Published - 2010 May

Keywords

Cellimmuno
Molimmuno
Signaling

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.immuni.2010.05.001

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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

Saijo, S, Ikeda, S, Yamabe, K, Kakuta, S, Ishigame, H, Akitsu, A, Fujikado, N, Kusaka, T, Kubo, S, Chung, SH, Komatsu, R, Miura, N, Adachi, Y, Ohno, N, Shibuya, K, Yamamoto, N, Kawakami, K, Yamasaki, S, Saito, T, Akira, S & Iwakura, Y 2010, 'Dectin-2 recognition of α-mannans and induction of Th17 cell differentiation is essential for host defense against candida albicans', Immunity, vol. 32, no. 5, pp. 681-691. https://doi.org/10.1016/j.immuni.2010.05.001

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title = "Dectin-2 recognition of α-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 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.",

keywords = "Cellimmuno, Molimmuno, Signaling",

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

note = "Funding Information: We deeply thank G.N. Barber for critical reading of the manuscript; N. Sato and A. Shibuya for their technical assistance; Y. Ishii for cell sorting; T. Chibana for SC5314 strain of C. albicans; and all of the members of our laboratory for animal care. This work was supported by CREST of the Japan Science and Technology Corporation, the Promotion of Basic Research Activities for Innovative Biosciences, Grants-in Aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, the Health Science Research Grant for Research on Emerging and Re-emerging Infectious Diseases, The Health Science Research Grant for Measures for Intractable Diseases from Ministry of Health, Labour, and Welfare of Japan, and The Grant of the Strategic Basis on Research Grounds from Ministry of Education, Culture, Sports, Science, and Technology of Japan. ",

year = "2010",

month = may,

doi = "10.1016/j.immuni.2010.05.001",

language = "English",

volume = "32",

pages = "681--691",

journal = "Immunity",

issn = "1074-7613",

publisher = "Cell Press",

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T1 - Dectin-2 recognition of α-mannans and induction of Th17 cell differentiation is essential for host defense against candida albicans

AU - Saijo, Shinobu

AU - Ikeda, Satoshi

AU - Yamabe, Keiko

AU - Kakuta, Shigeru

AU - Ishigame, Harumichi

AU - Akitsu, Aoi

AU - Fujikado, Noriyuki

AU - Kusaka, Toshimasa

AU - Kubo, Sachiko

AU - Chung, Soo hyun

AU - Komatsu, Ryohei

AU - Miura, Noriko

AU - Adachi, Yoshiyuki

AU - Ohno, Naohito

AU - Shibuya, Kazutoshi

AU - Yamamoto, Natsuo

AU - Kawakami, Kazuyoshi

AU - Yamasaki, Sho

AU - Saito, Takashi

AU - Akira, Shizuo

AU - Iwakura, Yoichiro

N1 - Funding Information: We deeply thank G.N. Barber for critical reading of the manuscript; N. Sato and A. Shibuya for their technical assistance; Y. Ishii for cell sorting; T. Chibana for SC5314 strain of C. albicans; and all of the members of our laboratory for animal care. This work was supported by CREST of the Japan Science and Technology Corporation, the Promotion of Basic Research Activities for Innovative Biosciences, Grants-in Aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, the Health Science Research Grant for Research on Emerging and Re-emerging Infectious Diseases, The Health Science Research Grant for Measures for Intractable Diseases from Ministry of Health, Labour, and Welfare of Japan, and The Grant of the Strategic Basis on Research Grounds from Ministry of Education, Culture, Sports, Science, and Technology of Japan.

PY - 2010/5

Y1 - 2010/5

N2 - 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.

AB - 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.

KW - Cellimmuno

KW - Molimmuno

KW - Signaling

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U2 - 10.1016/j.immuni.2010.05.001

DO - 10.1016/j.immuni.2010.05.001

M3 - Article

C2 - 20493731

AN - SCOPUS:77953289487

SN - 1074-7613

VL - 32

SP - 681

EP - 691

JO - Immunity

JF - Immunity

IS - 5

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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