Dectin-2 deficiency promotes Th2 response and mucin production in the lungs after pulmonary infection with Cryptococcus neoformans

Yuri Nakamura, Ko Sato, Hideki Yamamoto, Kana Matsumura, Ikumi Matsumoto, Toshiki Nomura, Tomomitsu Miyasaka, Keiko Ishii, Emi Kanno, Masahiro Tachi, Shou Yamasaki, Shinobu Saijo, Yoichiro Iwakura, Kazuyoshi Kawakami

    Research output: Contribution to journalArticle

    27 Citations (Scopus)

    Abstract

    Dectin-2 is a C-type lectin receptor that recognizes high mannose polysaccharides. Cryptococcus neoformans, a yeast-form fungal pathogen, is rich in polysaccharides in its cell wall and capsule. In the present study, we analyzed the role of Dectin-2 in the host defense against C. neoformans infection. In Dectin-2 gene-disrupted (knockout) (Dectin-2KO) mice, the clearance of this fungus and the inflammatory response, as shown by histological analysis and accumulation of leukocytes in infected lungs, were comparable to those in wild-type (WT) mice. The production of type 2 helper T (Th2) cytokines in lungs was higher in Dectin-2KO mice than inWTmice after infection, whereas there was no difference in the levels of production of Th1, Th17, and proinflammatory cytokines between these mice. Mucin production was significantly increased in Dectin-2KO mice, and this increase was reversed by administration of anti-interleukin 4 (IL-4) monoclonal antibody (MAb). The levels of expression ofβ1-defensin, cathelicidin, surfactant protein A (Sp-A), and Sp-D in infected lungs were comparable between these mice. In in vitro experiments, IL-12p40 and tumor necrosis factor alpha (TNF-α) production and expression of CD86 and major histocompatibility complex (MHC) class II by bone marrow-derived dendritic cells and alveolar macrophages were completely abrogated in Dectin-2KO mice. Finally, the disrupted lysates of C. neoformans, but not of whole yeast cells, activated Dectin-2-triggered signaling in an assay with nuclear factor of activated T cells (NFAT)-green fluorescent protein (GFP) reporter cells expressing this receptor. These results suggest that Dectin-2 may oppose the Th2 response and IL-4-dependent mucin production in the lungs after infection with C. neoformans, and it may not be required for the production of Th1, Th17, and proinflammatory cytokines or for clearance of this fungal pathogen.

    Original languageEnglish
    Pages (from-to)671-681
    Number of pages11
    JournalInfection and Immunity
    Volume83
    Issue number2
    DOIs
    Publication statusPublished - Jan 1 2015

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    Cryptococcus neoformans
    Mucins
    Lung
    Infection
    Cytokines
    Interleukin-4
    Polysaccharides
    Yeasts
    Interleukin-12 Subunit p40
    Pulmonary Surfactant-Associated Protein A
    NFATC Transcription Factors
    C-Type Lectins
    Defensins
    Gene Knockout Techniques
    Alveolar Macrophages
    Mannose
    Green Fluorescent Proteins
    mouse dectin-2
    Major Histocompatibility Complex
    Dendritic Cells

    All Science Journal Classification (ASJC) codes

    • Parasitology
    • Microbiology
    • Immunology
    • Infectious Diseases

    Cite this

    Dectin-2 deficiency promotes Th2 response and mucin production in the lungs after pulmonary infection with Cryptococcus neoformans. / Nakamura, Yuri; Sato, Ko; Yamamoto, Hideki; Matsumura, Kana; Matsumoto, Ikumi; Nomura, Toshiki; Miyasaka, Tomomitsu; Ishii, Keiko; Kanno, Emi; Tachi, Masahiro; Yamasaki, Shou; Saijo, Shinobu; Iwakura, Yoichiro; Kawakami, Kazuyoshi.

    In: Infection and Immunity, Vol. 83, No. 2, 01.01.2015, p. 671-681.

    Research output: Contribution to journalArticle

    Nakamura, Y, Sato, K, Yamamoto, H, Matsumura, K, Matsumoto, I, Nomura, T, Miyasaka, T, Ishii, K, Kanno, E, Tachi, M, Yamasaki, S, Saijo, S, Iwakura, Y & Kawakami, K 2015, 'Dectin-2 deficiency promotes Th2 response and mucin production in the lungs after pulmonary infection with Cryptococcus neoformans', Infection and Immunity, vol. 83, no. 2, pp. 671-681. https://doi.org/10.1128/IAI.02835-14
    Nakamura, Yuri ; Sato, Ko ; Yamamoto, Hideki ; Matsumura, Kana ; Matsumoto, Ikumi ; Nomura, Toshiki ; Miyasaka, Tomomitsu ; Ishii, Keiko ; Kanno, Emi ; Tachi, Masahiro ; Yamasaki, Shou ; Saijo, Shinobu ; Iwakura, Yoichiro ; Kawakami, Kazuyoshi. / Dectin-2 deficiency promotes Th2 response and mucin production in the lungs after pulmonary infection with Cryptococcus neoformans. In: Infection and Immunity. 2015 ; Vol. 83, No. 2. pp. 671-681.
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    abstract = "Dectin-2 is a C-type lectin receptor that recognizes high mannose polysaccharides. Cryptococcus neoformans, a yeast-form fungal pathogen, is rich in polysaccharides in its cell wall and capsule. In the present study, we analyzed the role of Dectin-2 in the host defense against C. neoformans infection. In Dectin-2 gene-disrupted (knockout) (Dectin-2KO) mice, the clearance of this fungus and the inflammatory response, as shown by histological analysis and accumulation of leukocytes in infected lungs, were comparable to those in wild-type (WT) mice. The production of type 2 helper T (Th2) cytokines in lungs was higher in Dectin-2KO mice than inWTmice after infection, whereas there was no difference in the levels of production of Th1, Th17, and proinflammatory cytokines between these mice. Mucin production was significantly increased in Dectin-2KO mice, and this increase was reversed by administration of anti-interleukin 4 (IL-4) monoclonal antibody (MAb). The levels of expression ofβ1-defensin, cathelicidin, surfactant protein A (Sp-A), and Sp-D in infected lungs were comparable between these mice. In in vitro experiments, IL-12p40 and tumor necrosis factor alpha (TNF-α) production and expression of CD86 and major histocompatibility complex (MHC) class II by bone marrow-derived dendritic cells and alveolar macrophages were completely abrogated in Dectin-2KO mice. Finally, the disrupted lysates of C. neoformans, but not of whole yeast cells, activated Dectin-2-triggered signaling in an assay with nuclear factor of activated T cells (NFAT)-green fluorescent protein (GFP) reporter cells expressing this receptor. These results suggest that Dectin-2 may oppose the Th2 response and IL-4-dependent mucin production in the lungs after infection with C. neoformans, and it may not be required for the production of Th1, Th17, and proinflammatory cytokines or for clearance of this fungal pathogen.",
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    AU - Matsumura, Kana

    AU - Matsumoto, Ikumi

    AU - Nomura, Toshiki

    AU - Miyasaka, Tomomitsu

    AU - Ishii, Keiko

    AU - Kanno, Emi

    AU - Tachi, Masahiro

    AU - Yamasaki, Shou

    AU - Saijo, Shinobu

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