Alveolar macrophages critically control infection by seasonal human coronavirus OC43 to avoid severe pneumonia
Xuan Zhong,
Tian Xie,
Su-Yun Wang,
Zhi-Sheng Xu,
Xin-Xin Chi,
Qiao-Shuai Lan,
Bo-Wen Xie,
Qin-Li Sun,
Lei Yuan,
Qiu-Yan Lan,
Zi-Xuan Zhao,
Bi-Rui Pan,
Han Feng,
Lu Lu,
Yan-Yi Wang,
Xiaohu Wang,
Chen Dong
Affiliations
Xuan Zhong
Institute for Immunology and School of Basic Medical Sciences, Tsinghua University, Beijing 100084, China; Tsinghua-Peking Center for Life Sciences, Beijing 100084, China
Tian Xie
Institute for Immunology and School of Basic Medical Sciences, Tsinghua University, Beijing 100084, China
Su-Yun Wang
Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430207, China
Zhi-Sheng Xu
Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430207, China
Xin-Xin Chi
Institute for Immunology and School of Basic Medical Sciences, Tsinghua University, Beijing 100084, China
Qiao-Shuai Lan
MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
Bo-Wen Xie
Institute for Immunology and School of Basic Medical Sciences, Tsinghua University, Beijing 100084, China; Tsinghua-Peking Center for Life Sciences, Beijing 100084, China
Qin-Li Sun
Institute for Immunology and School of Basic Medical Sciences, Tsinghua University, Beijing 100084, China
Lei Yuan
Institute for Immunology and School of Basic Medical Sciences, Tsinghua University, Beijing 100084, China
Qiu-Yan Lan
Institute for Immunology and School of Basic Medical Sciences, Tsinghua University, Beijing 100084, China
Zi-Xuan Zhao
Institute for Immunology and School of Basic Medical Sciences, Tsinghua University, Beijing 100084, China
Bi-Rui Pan
Institute for Immunology and School of Basic Medical Sciences, Tsinghua University, Beijing 100084, China
Han Feng
Institute for Immunology and School of Basic Medical Sciences, Tsinghua University, Beijing 100084, China
Lu Lu
MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
Yan-Yi Wang
Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430207, China
Xiaohu Wang
Institute for Immunology and School of Basic Medical Sciences, Tsinghua University, Beijing 100084, China
Chen Dong
Research Unit of Immune Regulation and Immune Diseases of Chinese Academy of Medical Sciences, Shanghai Jiao Tong University School of Medicine-Affiliated Renji Hospital, Shanghai 200127, China; Westlake University School of Medicine, Hangzhou, Zhejiang 310030, China; Corresponding author
Summary: Seasonal coronaviruses, similar to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), only cause severe respiratory symptoms in a small fraction of infected individuals. However, the host factors that determine the variable responses to coronavirus infection remain unclear. Here, we use seasonal human coronavirus OC43 (HCoV-OC43) infection as an asymptomatic model that triggers both innate and adaptive immune responses in mice. Interestingly, innate sensing pathways as well as adaptive immune cells are not essential in protection against HCoV-OC43. Instead, alveolar macrophage (AMΦ) deficiency in mice results in COVID-19-like severe pneumonia post HCoV-OC43 infection, with abundant neutrophil infiltration, neutrophil extracellular trap (NET) release, and exaggerated pro-inflammatory cytokine production. Mechanistically, AMΦ efficiently phagocytose HCoV-OC43, effectively blocking virus spread, whereas, in their absence, HCoV-OC43 triggers Toll-like receptor (TLR)-dependent chemokine production to cause pneumonia. These findings reveal the central role of AMΦ in defending against seasonal HCoV-OC43 with clinical implications for human immunopathology associated with coronavirus infection.
