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Induction of alarmin S100A8/A9 mediates activation of aberrant neutrophils in the pathogenesis of COVID-19, Cell Host & Microbe, 25 Dec 2020

发布时间:2020年12月25日

Cell Host & Microbe, 25 December, 2021, DOI:

Induction of alarmin S100A8/A9 mediates activation of aberrant neutrophils in the pathogenesis of COVID-19

Qirui Guo, Yingchi Zhao, Junhong Li, Jiangning Liu, Xiuhong Yang, Xuefei Guo, Ming Kuang, Huawei Xia, Zeming Zhang, Lili Cao, Yujie Luo, Linlin Bao, Xiao Wang, Xuemei Wei, Wei Deng, Nan Wang, Luoying Chen, Jingxuan Chen, Hua Zhu, Ran Gao, Chuan Qin, Xiangxi Wang, Fuping You

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses an unprecedented public health crisis. Evidence suggests that SARS-CoV-2 infection causes dysregulation of the immune system. However, the unique signature of early immune responses remains elusive. We characterized the transcriptome of rhesus macaques and mice infected with SARS-CoV-2. Alarmin S100A8 was robustly induced in SARS-CoV-2-infected animal models as well as in COVID-19 patients. Paquinimod, a specific inhibitor of S100A8/A9, could rescue the pneumonia with substantial reduction of viral loads in SARS-CoV-2-infected mice. Remarkably, Paquinimod treatment resulted in almost 100% survival in a lethal model of mouse coronavirus infection using the mouse hepatitis virus (MHV). A group of neutrophils that contributes to the uncontrolled pathological damage and onset of COVID-19 was dramatically induced by coronavirus infection. Paquinimod treatment could reduce these neutrophils and regain anti-viral responses, unveiling key roles of S100A8/A9 and aberrant neutrophils in the pathogenesis of COVID-19, highlighting new opportunities for therapeutic intervention.

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相关报道:http://www.wnpn.com.cn/kyjz/zxdt/202101/t20210111_5854590.html

 

 

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