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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 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

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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