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Protective Role of Naturally Occurring Interleukin-17A-Producing gammadelta T Cells in the Lung at the Early Stage of Systemic Candidiasis in Mice



Protective Role of Naturally Occurring Interleukin-17A-Producing gammadelta T Cells in the Lung at the Early Stage of Systemic Candidiasis in Mice







Interleukin-17A (IL-17A)-producing 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 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 T cell population in the lung, and C 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 T cells. Thus, our study demonstrated a novel role of naturally occurring IL-17A-producing T cells in the first line of host defense against C. albicans infection.

Accession: 036231717

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