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, Shou Yamasaki, Takashi Saito, Shizuo AkiraYoichiro Iwakura

    Research output: Contribution to journalArticle

    428 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 1 2010

    Fingerprint

    Mannans
    Th17 Cells
    Candida albicans
    Cell Differentiation
    Cytokines
    Dendritic Cells
    Yeasts
    C-Type Lectins
    Interleukin-23
    Interleukin-17
    Hyphae
    Interleukin-1
    Lectins
    Phosphotransferases
    Macrophages
    mouse dectin-2
    Genes

    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Immunology
    • Infectious Diseases

    Cite this

    Dectin-2 recognition of α-mannans and induction of Th17 cell differentiation is essential for host defense against candida albicans. / 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, Shou; Saito, Takashi; Akira, Shizuo; Iwakura, Yoichiro.

    In: Immunity, Vol. 32, No. 5, 01.05.2010, p. 681-691.

    Research output: Contribution to journalArticle

    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
    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, Shou ; Saito, Takashi ; Akira, Shizuo ; Iwakura, Yoichiro. / Dectin-2 recognition of α-mannans and induction of Th17 cell differentiation is essential for host defense against candida albicans. In: Immunity. 2010 ; Vol. 32, No. 5. pp. 681-691.
    @article{c2e7af84abf8458db6bf6d22d01c132a,
    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.",
    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 Shou Yamasaki and Takashi Saito and Shizuo Akira and Yoichiro Iwakura",
    year = "2010",
    month = "5",
    day = "1",
    doi = "10.1016/j.immuni.2010.05.001",
    language = "English",
    volume = "32",
    pages = "681--691",
    journal = "Immunity",
    issn = "1074-7613",
    publisher = "Cell Press",
    number = "5",

    }

    TY - JOUR

    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, Shou

    AU - Saito, Takashi

    AU - Akira, Shizuo

    AU - Iwakura, Yoichiro

    PY - 2010/5/1

    Y1 - 2010/5/1

    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.

    UR - http://www.scopus.com/inward/record.url?scp=77953289487&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=77953289487&partnerID=8YFLogxK

    U2 - 10.1016/j.immuni.2010.05.001

    DO - 10.1016/j.immuni.2010.05.001

    M3 - Article

    C2 - 20493731

    AN - SCOPUS:77953289487

    VL - 32

    SP - 681

    EP - 691

    JO - Immunity

    JF - Immunity

    SN - 1074-7613

    IS - 5

    ER -