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Cryptococcus deneoformans is an opportunistic intracellular growth fungal pathogen that frequently causes fatal meningoencephalitis in patients with impaired immune responses. In the current study, we analyzed the role of IL-17A in the host defense against C. deneoformans infection. IL-17A was quickly produced by \u03b3\u03b4T cells at an innate immune phase in infected lungs. In IL-17A gene\u2013disrupted mice, clearance of this fungal pathogen and the host immune response mediated by Th1 cells were significantly accelerated in infected lungs compared with wild-type mice. Similarly, killing of this fungus and production of inducible NO synthase and TNF-\u03b1 were significantly enhanced in IL-17A gene\u2013disrupted mice. In addition, elimination of this fungal pathogen, Th1 response, and expression of IL-12R\u03b22 and IFN-\u03b3 in NK and NKT cells were significantly suppressed by treatment with rIL-17A. The production of IL-12p40 and TNF-\u03b1 from bone marrow\u2013derived dendritic cells stimulated with C. deneoformans was significantly suppressed by rIL-17A. In addition, rIL-17A attenuated Th1 cell differentiation in splenocytes from transgenic mice highly expressing TCR for mannoprotein 98, a cryptococcal Ag, upon stimulation with recombinant mannoprotein 98. These data suggest that IL-17A may be involved in the negative regulation of the local host defense against C. deneoformans infection through suppression of the Th1 response.<\/jats:p>","DOI":"10.4049\/jimmunol.1901238","type":"journal-article","created":{"date-parts":[[2020,6,19]],"date-time":"2020-06-19T18:55:14Z","timestamp":1592592914000},"page":"686-698","source":"Crossref","is-referenced-by-count":31,"title":["Production of IL-17A at Innate Immune Phase Leads to Decreased Th1 Immune Response and Attenuated Host Defense against Infection with <i>Cryptococcus deneoformans<\/i>"],"prefix":"10.1093","volume":"205","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5548-6285","authenticated-orcid":false,"given":"Ko","family":"Sato","sequence":"first","affiliation":[{"name":"Department of Intelligent Network for Infection Control, Tohoku University Graduate School of Medicine , Sendai, Miyagi 980-8575 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