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Blockade of the C5a-C5aR axis alleviates lung damage in hDPP4-transgenic mice infected with MERS-CoV 期刊论文

编号：

54964f85-2127-4090-896a-1ea85220622b
作者：

Jiang, Yuting^[1];Zhao, Guangyu^[1];Song, Nianping^[1];Li, Pei^[1];Chen, Yuehong^[1];Guo, Yan^[1];Li, Junfeng^[1];Du, Lanying^[2];Jiang, Shibo(姜世勃)^[2,3]Guo, Renfeng^[4];Sun, Shihui^[1];Zhou, Yusen^[1];
语种：

English
期刊：

EMERGING MICROBES & INFECTIONS ISSN：2222-1751 2018 年 7 卷 ; APR 24
收录：
摘要：

The pathogenesis of highly pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV) remains poorly understood. In a previous study, we established an hDPP4-transgenic (hDPP4-Tg) mouse model in which MERS-CoV infection causes severe acute respiratory failure and high mortality accompanied by an elevated secretion of cytokines and chemokines. Since excessive complement activation is an important factor that contributes to acute lung injury after viral infection, in this study, we investigated the role of complement in MERS-CoV-induced lung damage. Our study showed that complement was excessively activated in MERS-CoV-infected hDPP4-Tg mice through observations of increased concentrations of the C5a and C5b-9 complement activation products in sera and lung tissues, respectively. Interestingly, blocking C5a production by targeting its receptor, C5aR, alleviated lung and spleen tissue damage and reduced inflammatory responses. More importantly, anti-C5aR antibody treatment led to decreased viral replication in lung tissues. Furthermore, compared with the sham treatment control, apoptosis of splenic cells was less pronounced in the splenic white pulp of treated mice, and greater number of proliferating splenic cells, particularly in the red pulp, was observed. These data indicate that (1) dysregulated host immune responses contribute to the severe outcome of MERS; (2) excessive complement activation, triggered by MERS-CoV infection, promote such dysregulation; and (3) blockade of the C5a-C5aR axis lead to the decreased tissue damage induced by MERS-CoV infection, as manifested by reduced apoptosis and T cell regeneration in the spleen. Therefore, the results of this study suggest a new strategy for clinical intervention and adjunctive treatment in MERS-CoV cases.
推荐引用方式
GB/T 7714：

Jiang Yuting,Zhao Guangyu,Song Nianping, et al. Blockade of the C5a-C5aR axis alleviates lung damage in hDPP4-transgenic mice infected with MERS-CoV [J].EMERGING MICROBES & INFECTIONS,2018,7.
APA：

Jiang Yuting,Zhao Guangyu,Song Nianping,Li Pei,&Zhou Yusen.(2018).Blockade of the C5a-C5aR axis alleviates lung damage in hDPP4-transgenic mice infected with MERS-CoV .EMERGING MICROBES & INFECTIONS,7.
MLA：

Jiang Yuting, et al. "Blockade of the C5a-C5aR axis alleviates lung damage in hDPP4-transgenic mice infected with MERS-CoV" .EMERGING MICROBES & INFECTIONS 7(2018).

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