IL-17A Produced by Neutrophils Protects against Pneumonic Plague through Orchestrating IFN-γ-Activated Macrophage Programming

被引：30

作者：

Bi, Yujing ^{[1
]}

Zhou, Jiyuan ^{[1
]}

Yang, Hui ^{[2
,3
]}

Wang, Xiao ^{[2
,3
]}

Zhang, Xuecan ^{[1
]}

Wang, Qiong ^{[1
]}

Wu, Xiaohong ^{[1
]}

Han, Yanping ^{[1
]}

Song, Yajun ^{[1
]}

Tan, Yafang ^{[1
]}

Du, Zongmin ^{[1
]}

Yang, Huiying ^{[1
]}

Zhou, Dongsheng ^{[1
]}

Cui, Yujun ^{[1
]}

Zhou, Lei ^{[1
]}

Yan, Yanfeng ^{[1
]}

Zhang, Pingping ^{[1
]}

Guo, Zhaobiao ^{[1
]}

Wang, Xiaoyi ^{[1
]}

Liu, Guangwei ^{[2
,3
]}

Yang, Ruifu ^{[1
]}

机构：

[1] Beijing Inst Microbiol & Epidemiol, State Key Lab Pathogen & Biosecur, Beijing 100071, Peoples R China

[2] Fudan Univ, Minist Hlth, Minist Educ, Key Lab Med Mol Virol, Shanghai 200032, Peoples R China

[3] Fudan Univ, Biotherapy Res Ctr, Shanghai 200032, Peoples R China

来源：

JOURNAL OF IMMUNOLOGY | 2014年 / 192卷 / 02期

关键词：

YERSINIA-PESTIS; LUNG INFLAMMATION; T-CELLS; DELTA T; INFECTION; RECRUITMENT; TH17; RESPONSES; IMMUNITY; DEFENSE;

D O I：

10.4049/jimmunol.1301687

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

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-gamma treatment or IFN-gamma-activated M1 macrophage transfer could significantly mitigate the aggravated infection of IL-17A(-/-) mice. Finally, we showed that IL-17A and IFN-gamma 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.

引用

页码：704 / 713

页数：10

共 56 条

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