title: IL-17A produced by neutrophils protects against pneumonic plague through orchestrating IFN-γ-activated macrophage programming.
abstract: Innate immune cells, including neutrophils and macrophages, are critically involved in host antimicrobial defense responses. Intrinsic regulatory mechanisms controlling neutrophil and macrophage activities are poorly defined. 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's defense against pneumonic plague. Mechanistically, IFN-γ treatment or IFN-γ-activated M1 macrophage transfer could significantly mitigate the aggravated infection of IL-17A(-/-) mice. Finally, we showed that IL-17A and IFN-γ 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.
authors: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China;
authors: Yujing
authors: Y
authors: Bi
authors: Jiyuan
authors: J
authors: Zhou
authors: Hui
authors: H
authors: Yang
authors: Xiao
authors: X
authors: Wang
authors: Xuecan
authors: X
authors: Zhang
authors: Qiong
authors: Q
authors: Wang
authors: Xiaohong
authors: X
authors: Wu
authors: Yanping
authors: Y
authors: Han
authors: Yajun
authors: Y
authors: Song
authors: Yafang
authors: Y
authors: Tan
authors: Zongmin
authors: Z
authors: Du
authors: Huiying
authors: H
authors: Yang
authors: Dongsheng
authors: D
authors: Zhou
authors: Yujun
authors: Y
authors: Cui
authors: Lei
authors: L
authors: Zhou
authors: Yanfeng
authors: Y
authors: Yan
authors: Pingping
authors: P
authors: Zhang
authors: Zhaobiao
authors: Z
authors: Guo
authors: Xiaoyi
authors: X
authors: Wang
authors: Guangwei
authors: G
authors: Liu
authors: Ruifu
authors: R
authors: Yang
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000276:immunology / Q000378:metabolism; D039481:CD11b Antigen / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism*; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D010930:Plague / Q000276:immunology* / Q000378:metabolism; D053722:Receptors, Interleukin-17 / Q000276:immunology / Q000378:metabolism
chemical_list: D000950:Antigens, Ly; D039481:CD11b Antigen; C491673:Il17ra protein, mouse; D020381:Interleukin-17; C480309:Ly6G antigen, mouse; D053722:Receptors, Interleukin-17; D007371:Interferon-gamma