title: Protective role of naturally occurring interleukin-17A-producing γδ T cells in the lung at the early stage of systemic candidiasis in mice.
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.
authors.affiliation: Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Dejima
authors.forename: Kensuke
authors.initials: K
authors.lastname: Shibata
authors.forename: Hisakata
authors.initials: H
authors.lastname: Yamada
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Hara
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Seiji
authors.initials: S
authors.lastname: Naito
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Yoshikai
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D053468:CARD Signaling Adaptor Proteins; D002177:Candidiasis / Q000276:immunology*; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D053759:Interleukin-23 / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D009504:Neutrophils / Q000502:physiology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D016176:T-Lymphocyte Subsets / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D053468:CARD Signaling Adaptor Proteins; C513280:Card9 protein, mouse; D020381:Interleukin-17; D053759:Interleukin-23; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016692:Receptors, Antigen, T-Cell, gamma-delta; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2