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

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 mul...

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Main Authors: 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, Xuetao Cao
Format: Article
Language:English
Published: Nature Publishing Group 2024-10-01
Series:Cell Discovery
Online Access:https://doi.org/10.1038/s41421-024-00734-4
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author 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
Xuetao Cao
author_facet 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
Xuetao Cao
author_sort Boyi Cong
collection DOAJ
description 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.
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publishDate 2024-10-01
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series Cell Discovery
spelling doaj-art-733967fd5aa649879b1739b6ee8d62842024-11-10T12:06:22ZengNature Publishing GroupCell Discovery2056-59682024-10-0110111310.1038/s41421-024-00734-4Single-cell spatiotemporal analysis of the lungs reveals Slamf9 + macrophages involved in viral clearance and inflammation resolutionBoyi Cong0Xuan Dong1Zongheng Yang2Pin Yu3Yangyang Chai4Jiaqi Liu5Meihan Zhang6Yupeng Zang7Jingmin Kang8Yu Feng9Yi Liu10Weimin Feng11Dehe Wang12Wei Deng13Fengdi Li14Zhiqi Song15Ziqiao Wang16Xiaosu Chen17Hua Qin18Qinyi Yu19Zhiqing Li20Shuxun Liu21Xun Xu22Nanshan Zhong23Xianwen Ren24Chuan Qin25Longqi Liu26Jian Wang27Xuetao Cao28State Key Laboratory of Medicinal Chemical Biology, Institute of Immunology, College of Life Sciences, Nankai UniversityBGI-ShenzhenDepartment of Immunology, Center for Immunotherapy, Peking Union Medical College, Chinese Academy of Medical SciencesInstitute of Laboratory Animal Sciences, Chinese Academy of Medical SciencesDepartment of Immunology, Center for Immunotherapy, Peking Union Medical College, Chinese Academy of Medical SciencesDepartment of Immunology, Center for Immunotherapy, Peking Union Medical College, Chinese Academy of Medical SciencesState Key Laboratory of Medicinal Chemical Biology, Institute of Immunology, College of Life Sciences, Nankai UniversityBGI-ShenzhenBGI-ShenzhenBGI-ShenzhenBGI-ShenzhenBGI-ShenzhenChangping LaboratoryInstitute of Laboratory Animal Sciences, Chinese Academy of Medical SciencesInstitute of Laboratory Animal Sciences, Chinese Academy of Medical SciencesInstitute of Laboratory Animal Sciences, Chinese Academy of Medical SciencesDepartment of Immunology, Center for Immunotherapy, Peking Union Medical College, Chinese Academy of Medical SciencesState Key Laboratory of Medicinal Chemical Biology, Institute of Immunology, College of Life Sciences, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology, Institute of Immunology, College of Life Sciences, Nankai UniversityInstitute of Immunology, Zhejiang University School of MedicineNational Key Laboratory of Immunity and Inflammation, Institute of Immunology, Navy Medical UniversityNational Key Laboratory of Immunity and Inflammation, Institute of Immunology, Navy Medical UniversityBGI-ShenzhenGuangzhou LaboratoryChangping LaboratoryInstitute of Laboratory Animal Sciences, Chinese Academy of Medical SciencesBGI-ShenzhenBGI-ShenzhenState Key Laboratory of Medicinal Chemical Biology, Institute of Immunology, College of Life Sciences, Nankai UniversityAbstract 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.https://doi.org/10.1038/s41421-024-00734-4
spellingShingle 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
Xuetao Cao
Single-cell spatiotemporal analysis of the lungs reveals Slamf9 + macrophages involved in viral clearance and inflammation resolution
Cell Discovery
title Single-cell spatiotemporal analysis of the lungs reveals Slamf9 + macrophages involved in viral clearance and inflammation resolution
title_full Single-cell spatiotemporal analysis of the lungs reveals Slamf9 + macrophages involved in viral clearance and inflammation resolution
title_fullStr Single-cell spatiotemporal analysis of the lungs reveals Slamf9 + macrophages involved in viral clearance and inflammation resolution
title_full_unstemmed Single-cell spatiotemporal analysis of the lungs reveals Slamf9 + macrophages involved in viral clearance and inflammation resolution
title_short Single-cell spatiotemporal analysis of the lungs reveals Slamf9 + macrophages involved in viral clearance and inflammation resolution
title_sort single cell spatiotemporal analysis of the lungs reveals slamf9 macrophages involved in viral clearance and inflammation resolution
url https://doi.org/10.1038/s41421-024-00734-4
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