Single-cell spatiotemporal analysis of the lungs reveals Slamf9+ macrophages involved in viral clearance and inflammation resolution
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<sup>+</sup> macrophages, which are induced after SARS-CoV-2 infection and resistant to impairment caused by SARS-CoV-2. Slamf9<sup>+</sup> macrophages contain SARS-CoV-2, recruit and interact with Isg12<sup>+</sup>Cst7<sup>+</sup> neutrophils to clear the viruses. After viral clearance, Slamf9<sup>+</sup> macrophages differentiate into Trem2<sup>+</sup> and Fbp1<sup>+</sup> 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<sup>+</sup> macrophages and their coordination with neutrophils in post-injury tissue repair and inflammation resolution.
Authors
- Shuxun Liu (ORCID: https://orcid.org/0000-0002-6296-7538)
- Qinyi Yu
- Jingmin Kang (ORCID: https://orcid.org/0009-0006-5901-5268)
- Longqi Liu (ORCID: https://orcid.org/0000-0002-5828-5542)
- Xuetao Cao (ORCID: https://orcid.org/0000-0001-9677-7647)
- Yupeng Zang (ORCID: https://orcid.org/0000-0002-5098-1172)
- Dehe Wang (ORCID: https://orcid.org/0000-0001-6073-2295)
- Boyi Cong
- Zongheng Yang
- Hua Qin
- Xuan Dong (ORCID: https://orcid.org/0000-0003-4740-278X)
- Xianwen Ren (ORCID: https://orcid.org/0000-0002-8558-5401)
- Ziqiao Wang (ORCID: https://orcid.org/0000-0002-6720-4732)
- Xiaosu Chen (ORCID: https://orcid.org/0000-0001-9424-2219)
- Wei Deng (ORCID: https://orcid.org/0000-0002-1619-2313)
- Meihan Zhang
- Yi Liu (ORCID: https://orcid.org/0000-0002-3744-0590)
- Jian Wang (ORCID: https://orcid.org/0000-0002-9482-5227)
- Jiaqi Liu (ORCID: https://orcid.org/0000-0002-9775-2342)
- Xun Xu (ORCID: https://orcid.org/0000-0002-5338-5173)
- Yu Feng (ORCID: https://orcid.org/0009-0008-4746-1070)
- Zhiqing Li (ORCID: https://orcid.org/0000-0003-3208-5726)
- Pin Yü (ORCID: https://orcid.org/0000-0002-8744-1727)
- Yangyang Chai (ORCID: https://orcid.org/0000-0002-3646-7820)
- Zhiqi Song (ORCID: https://orcid.org/0000-0001-8628-2309)
- Weimin Feng (ORCID: https://orcid.org/0000-0002-0862-1640)
- Fengdi Li
- Chuan Qin
- Nanshan Zhong (ORCID: https://orcid.org/0009-0008-7677-2572)
Institutions
- BGI Group (China) (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Nankai University (CN)
- Peking Union Medical College Hospital (CN)
- Changchun Observatory (CN)
- Institute of Laboratory Animal Science (CN)
- Zhejiang University (CN)
Publication Details
- Journal
- Cell Discovery
- Published
- 2024-10-16
- DOI
- https://doi.org/10.1038/s41421-024-00734-4
- Citations
- 21
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 4.91
Funders
- National Natural Science Foundation of China