Single-cell spatiotemporal analysis of the lungs reveals Slamf9+ macrophages involved in viral clearance and inflammation resolution

被引:7
作者
Cong, Boyi [1 ,2 ]
Dong, Xuan [3 ]
Yang, Zongheng [2 ]
Yu, Pin [4 ]
Chai, Yangyang [2 ]
Liu, Jiaqi [2 ]
Zhang, Meihan [1 ]
Zang, Yupeng [3 ]
Kang, Jingmin [3 ]
Feng, Yu [3 ]
Liu, Yi [3 ]
Feng, Weimin [3 ]
Wang, Dehe [5 ]
Deng, Wei [4 ]
Li, Fengdi [4 ]
Song, Zhiqi [4 ]
Wang, Ziqiao [2 ]
Chen, Xiaosu [1 ]
Qin, Hua [1 ]
Yu, Qinyi [6 ]
Li, Zhiqing [7 ,8 ]
Liu, Shuxun [7 ,8 ]
Xu, Xun [3 ]
Zhong, Nanshan [8 ]
Ren, Xianwen [5 ]
Qin, Chuan [4 ]
Liu, Longqi [3 ]
Wang, Jian [3 ]
Cao, Xuetao [1 ,2 ]
机构
[1] Nankai Univ, Inst Immunol, Coll Life Sci, State Key Lab Med Chem Biol, Tianjin, Peoples R China
[2] Chinese Acad Med Sci, Peking Union Med Coll, Ctr Immunotherapy, Dept Immunol, Beijing, Peoples R China
[3] BGI Shenzhen, Shenzhen, Guangdong, Peoples R China
[4] Chinese Acad Med Sci, Inst Lab Anim Sci, Beijing, Peoples R China
[5] Changping Lab, Beijing, Peoples R China
[6] Zhejiang Univ, Sch Med, Inst Immunol, Hangzhou, Zhejiang, Peoples R China
[7] Navy Med Univ, Inst Immunol, Natl Key Lab Immun & Inflammat, Shanghai, Peoples R China
[8] Guangzhou Lab, Guangzhou, Guangdong, Peoples R China
基金
中国国家自然科学基金; 国家重点研发计划;
关键词
SARS-COV-2; INFECTION; HAMSTERS; MODEL;
D O I
10.1038/s41421-024-00734-4
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
How the lung achieves immune homeostasis after a pulmonary infection is not fully understood. Here, we analyzed the spatiotemporal changes in the lungs over a 2-week natural recovery from severe pneumonia in a Syrian hamster model of SARS-CoV-2 infection. We find that SARS-CoV-2 infects multiple cell types and causes massive cell death at the early stage, including alveolar macrophages. We identify a group of monocyte-derived Slamf9(+) macrophages, which are induced after SARS-CoV-2 infection and resistant to impairment caused by SARS-CoV-2. Slamf9(+) macrophages contain SARS-CoV-2, recruit and interact with Isg12(+)Cst7(+) neutrophils to clear the viruses. After viral clearance, Slamf9(+) macrophages differentiate into Trem2(+) and Fbp1(+) macrophages, contributing to inflammation resolution at the late stage, and finally replenish alveolar macrophages. These findings are validated in a SARS-CoV-2-infected hACE2 mouse model and confirmed with publicly available human autopsy single-cell RNA-seq data, demonstrating the potential role of Slamf9+ macrophages and their coordination with neutrophils in post-injury tissue repair and inflammation resolution.
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页数:13
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