Protective role of naturally occurring interleukin-17A-producing γδ cells in the Lung at the early stage of systemic candidiasis in mice

Takashi Dejima, Kensuke Shibata, Hisakata Yamada, Hiromitsu Hara, Yoichiro Iwakura, Seiji Naito, Yasunobu Yoshikai

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Interleukin-17A (IL-17A)-producing γδ T cells differentiate in the fetal thymus and reside in the peripheral tissues, such as the lungs of naïve adult mice. We show here that naturally occurring γδ T cells play a protective role in the lung at a very early stage after systemic infection with Candida albicans. Selective depletion of neutrophils by in vivo administration of anti-Ly6G monoclonal antibody (MAb) impaired fungal clearance more prominently in the lung than in the kidney 24 h after intravenous infection with C. albicans. Rapid and transient production of IL-23 was detected in the lung at 12 h, preceding IL-17A production and the influx of neutrophils, which reached a peak at 24 h after infection. IL-17A knockout (KO) mice showed reduced infiltration of neutrophils concurrently with impaired fungal clearance in the lung after infection. The major source of IL-17A was the γδ T cell population in the lung, and Cδ KO mice showed little IL-17A production and reduced neutrophil infiltration after infection. Early IL-23 production in a TLR2/MyD88-dependent manner and IL-23-triggered tyrosine kinase 2 (Tyk2) signaling were essential for IL-17A production by γδ T cells. Thus, our study demonstrated a novel role of naturally occurring IL-17A-producing γδ T cells in the first line of host defense against C. albicans infection.

Original languageEnglish
Pages (from-to)4503-4510
Number of pages8
JournalInfection and Immunity
Volume79
Issue number11
DOIs
Publication statusPublished - Nov 1 2011

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All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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