Exacerbation of invasive candida albicans infection by commensal bacteria or a glycolipid through IFN- Produced in part by iNKT cells

Norihito Tarumoto, Yuki Kinjo, Naoki Kitano, Daisuke Sasai, Keigo Ueno, Akiko Okawara, Yuina Izawa, Minoru Shinozaki, Hiroshi Watarai, Masaru Taniguchi, Haruko Takeyama, Shigefumi Maesaki, Kazutoshi Shibuya, Yoshitsugu Miyazaki

    Research output: Contribution to journalArticle

    9 Citations (Scopus)

    Abstract

    Background. The commensal yeast Candida albicans is a major cause of invasive fungal infections. Despite treatment with antifungal agents, the mortality rate attributed to these types of infection is high. Although numerous cases have been reported regarding a poor outcome for patients with bacterial and C. albicans coinfection, the mechanisms by which the coinfecting bacteria exacerbate the C. albicans infection remain elusive.Methods and Results We evaluated how glycolipid-mediated activation of invariant natural killer T (iNKT) cells affects the clearance of C. albicans. Surprisingly, C. albicans-infected, glycolipid-treated mice exhibited significantly lower survival rates, increased fungal burden, and higher interleukin (IL)-6 production in the kidneys compared with control mice. Glycolipid-induced exacerbation of C. albicans infection was not observed in interferon-gamma knockout (IFN-KO) mice. In the C. albicans-infected, glycolipid-treated mice, the number of neutrophils in the blood and bone marrow dramatically decreased in an IFN--dependent manner. Furthermore, mice that were coinfected with C. albicans and nonfermentative gram-negative commensal bacteria exhibited increased fungal burden and inflammatory cytokine production in the kidneys that were dependent on IFN- and iNKT cells.Conclusions. Our results indicate that coinfecting commensal bacteria exacerbate C. albicans infection through IFN- produced, in part, by iNKT cells.

    Original languageEnglish
    Pages (from-to)799-810
    Number of pages12
    JournalJournal of Infectious Diseases
    Volume209
    Issue number5
    DOIs
    Publication statusPublished - 2014 Mar

    Fingerprint

    Natural Killer T-Cells
    Glycolipids
    Candida albicans
    Bacteria
    Infection
    Kidney
    Antifungal Agents
    Gram-Negative Bacteria
    Coinfection
    Knockout Mice
    Interferon-gamma
    Interleukin-6
    Neutrophils
    Survival Rate
    Yeasts
    Bone Marrow
    Cytokines
    Mortality

    Keywords

    • Candida albicans
    • commensal bacteria
    • glycolipid
    • iNKT cell
    • nonfermentative gram-negative bacteria

    ASJC Scopus subject areas

    • Infectious Diseases
    • Immunology and Allergy

    Cite this

    Exacerbation of invasive candida albicans infection by commensal bacteria or a glycolipid through IFN- Produced in part by iNKT cells. / Tarumoto, Norihito; Kinjo, Yuki; Kitano, Naoki; Sasai, Daisuke; Ueno, Keigo; Okawara, Akiko; Izawa, Yuina; Shinozaki, Minoru; Watarai, Hiroshi; Taniguchi, Masaru; Takeyama, Haruko; Maesaki, Shigefumi; Shibuya, Kazutoshi; Miyazaki, Yoshitsugu.

    In: Journal of Infectious Diseases, Vol. 209, No. 5, 03.2014, p. 799-810.

    Research output: Contribution to journalArticle

    Tarumoto, N, Kinjo, Y, Kitano, N, Sasai, D, Ueno, K, Okawara, A, Izawa, Y, Shinozaki, M, Watarai, H, Taniguchi, M, Takeyama, H, Maesaki, S, Shibuya, K & Miyazaki, Y 2014, 'Exacerbation of invasive candida albicans infection by commensal bacteria or a glycolipid through IFN- Produced in part by iNKT cells', Journal of Infectious Diseases, vol. 209, no. 5, pp. 799-810. https://doi.org/10.1093/infdis/jit534
    Tarumoto, Norihito ; Kinjo, Yuki ; Kitano, Naoki ; Sasai, Daisuke ; Ueno, Keigo ; Okawara, Akiko ; Izawa, Yuina ; Shinozaki, Minoru ; Watarai, Hiroshi ; Taniguchi, Masaru ; Takeyama, Haruko ; Maesaki, Shigefumi ; Shibuya, Kazutoshi ; Miyazaki, Yoshitsugu. / Exacerbation of invasive candida albicans infection by commensal bacteria or a glycolipid through IFN- Produced in part by iNKT cells. In: Journal of Infectious Diseases. 2014 ; Vol. 209, No. 5. pp. 799-810.
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    abstract = "Background. The commensal yeast Candida albicans is a major cause of invasive fungal infections. Despite treatment with antifungal agents, the mortality rate attributed to these types of infection is high. Although numerous cases have been reported regarding a poor outcome for patients with bacterial and C. albicans coinfection, the mechanisms by which the coinfecting bacteria exacerbate the C. albicans infection remain elusive.Methods and Results We evaluated how glycolipid-mediated activation of invariant natural killer T (iNKT) cells affects the clearance of C. albicans. Surprisingly, C. albicans-infected, glycolipid-treated mice exhibited significantly lower survival rates, increased fungal burden, and higher interleukin (IL)-6 production in the kidneys compared with control mice. Glycolipid-induced exacerbation of C. albicans infection was not observed in interferon-gamma knockout (IFN-KO) mice. In the C. albicans-infected, glycolipid-treated mice, the number of neutrophils in the blood and bone marrow dramatically decreased in an IFN--dependent manner. Furthermore, mice that were coinfected with C. albicans and nonfermentative gram-negative commensal bacteria exhibited increased fungal burden and inflammatory cytokine production in the kidneys that were dependent on IFN- and iNKT cells.Conclusions. Our results indicate that coinfecting commensal bacteria exacerbate C. albicans infection through IFN- produced, in part, by iNKT cells.",
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    AU - Kinjo, Yuki

    AU - Kitano, Naoki

    AU - Sasai, Daisuke

    AU - Ueno, Keigo

    AU - Okawara, Akiko

    AU - Izawa, Yuina

    AU - Shinozaki, Minoru

    AU - Watarai, Hiroshi

    AU - Taniguchi, Masaru

    AU - Takeyama, Haruko

    AU - Maesaki, Shigefumi

    AU - Shibuya, Kazutoshi

    AU - Miyazaki, Yoshitsugu

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    N2 - Background. The commensal yeast Candida albicans is a major cause of invasive fungal infections. Despite treatment with antifungal agents, the mortality rate attributed to these types of infection is high. Although numerous cases have been reported regarding a poor outcome for patients with bacterial and C. albicans coinfection, the mechanisms by which the coinfecting bacteria exacerbate the C. albicans infection remain elusive.Methods and Results We evaluated how glycolipid-mediated activation of invariant natural killer T (iNKT) cells affects the clearance of C. albicans. Surprisingly, C. albicans-infected, glycolipid-treated mice exhibited significantly lower survival rates, increased fungal burden, and higher interleukin (IL)-6 production in the kidneys compared with control mice. Glycolipid-induced exacerbation of C. albicans infection was not observed in interferon-gamma knockout (IFN-KO) mice. In the C. albicans-infected, glycolipid-treated mice, the number of neutrophils in the blood and bone marrow dramatically decreased in an IFN--dependent manner. Furthermore, mice that were coinfected with C. albicans and nonfermentative gram-negative commensal bacteria exhibited increased fungal burden and inflammatory cytokine production in the kidneys that were dependent on IFN- and iNKT cells.Conclusions. Our results indicate that coinfecting commensal bacteria exacerbate C. albicans infection through IFN- produced, in part, by iNKT cells.

    AB - Background. The commensal yeast Candida albicans is a major cause of invasive fungal infections. Despite treatment with antifungal agents, the mortality rate attributed to these types of infection is high. Although numerous cases have been reported regarding a poor outcome for patients with bacterial and C. albicans coinfection, the mechanisms by which the coinfecting bacteria exacerbate the C. albicans infection remain elusive.Methods and Results We evaluated how glycolipid-mediated activation of invariant natural killer T (iNKT) cells affects the clearance of C. albicans. Surprisingly, C. albicans-infected, glycolipid-treated mice exhibited significantly lower survival rates, increased fungal burden, and higher interleukin (IL)-6 production in the kidneys compared with control mice. Glycolipid-induced exacerbation of C. albicans infection was not observed in interferon-gamma knockout (IFN-KO) mice. In the C. albicans-infected, glycolipid-treated mice, the number of neutrophils in the blood and bone marrow dramatically decreased in an IFN--dependent manner. Furthermore, mice that were coinfected with C. albicans and nonfermentative gram-negative commensal bacteria exhibited increased fungal burden and inflammatory cytokine production in the kidneys that were dependent on IFN- and iNKT cells.Conclusions. Our results indicate that coinfecting commensal bacteria exacerbate C. albicans infection through IFN- produced, in part, by iNKT cells.

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