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

T Dejima, K Shibata, H Yamada, H Hara… - Infection and …, 2011 - Am Soc Microbiol
T Dejima, K Shibata, H Yamada, H Hara, Y Iwakura, S Naito, Y Yoshikai
Infection and immunity, 2011Am Soc Microbiol
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 …
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.
American Society for Microbiology