1. Single-cell spatiotemporal analysis of the lungs reveals Slamf9 + macrophages involved in viral clearance and inflammation resolution
- Author
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Boyi Cong, Xuan Dong, Zongheng Yang, Pin Yu, Yangyang Chai, Jiaqi Liu, Meihan Zhang, Yupeng Zang, Jingmin Kang, Yu Feng, Yi Liu, Weimin Feng, Dehe Wang, Wei Deng, Fengdi Li, Zhiqi Song, Ziqiao Wang, Xiaosu Chen, Hua Qin, Qinyi Yu, Zhiqing Li, Shuxun Liu, Xun Xu, Nanshan Zhong, Xianwen Ren, Chuan Qin, Longqi Liu, Jian Wang, and Xuetao Cao
- Subjects
Cytology ,QH573-671 - Abstract
Abstract 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.
- Published
- 2024
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