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In this study, we found that IL-17A, a natural signal factor, could provide protection against early pneumonic plague inflammation by coordinating the functions of neutrophils and programming of macrophages. The IL-17A level is promptly increased during the initial infection. Importantly, abrogation of IL-17A or IL-17AR significantly aggravated the infection, but mIL-17A treatment could significantly alleviate inflammatory injury, revealing that IL-17A is a critical requirement for early protection of infection. We also demonstrated that IL-17A was predominantly produced by CD11b+Ly6G+ neutrophils. Although IL-17A could not significantly affect the antimicrobial responses of neutrophils, it could target the proinflammatory macrophage (M1) programming and potentiate the M1\u2019s defense against pneumonic plague. Mechanistically, IFN-\u03b3 treatment or IFN-\u03b3\u2013activated M1 macrophage transfer could significantly mitigate the aggravated infection of IL-17A\u2212\/\u2212 mice. Finally, we showed that IL-17A and IFN-\u03b3 could synergistically promote macrophage anti-infection immunity. Thus, our findings identify a previously unrecognized function of IL-17A as an intrinsic regulator in coordinating neutrophil and macrophage antimicrobial activity to provide protection against acute pneumonic plague.<\/jats:p>","DOI":"10.4049\/jimmunol.1301687","type":"journal-article","created":{"date-parts":[[2013,12,14]],"date-time":"2013-12-14T03:19:59Z","timestamp":1386991199000},"page":"704-713","source":"Crossref","is-referenced-by-count":36,"title":["IL-17A Produced by Neutrophils Protects against Pneumonic Plague through Orchestrating IFN-\u03b3\u2013Activated Macrophage Programming"],"prefix":"10.1093","volume":"192","author":[{"given":"Yujing","family":"Bi","sequence":"first","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology , Beijing 100071,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyuan","family":"Zhou","sequence":"additional","affiliation":[{"name":"State 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