2. Academic Validation
  3. Alveolar macrophages critically control infection by seasonal human coronavirus OC43 to avoid severe pneumonia

Alveolar macrophages critically control infection by seasonal human coronavirus OC43 to avoid severe pneumonia

  • Cell Rep. 2025 Apr 22;44(4):115531. doi: 10.1016/j.celrep.2025.115531.
Xuan Zhong 1,  Tian Xie 2,  Su-Yun Wang 3,  Zhi-Sheng Xu 3,  Xin-Xin Chi 2,  Qiao-Shuai Lan 4,  Bo-Wen Xie 1,  Qin-Li Sun 2,  Lei Yuan 2,  Qiu-Yan Lan 2,  Zi-Xuan Zhao 2,  Bi-Rui Pan 2,  Han Feng 2,  Lu Lu 4,  Yan-Yi Wang 3,  Xiaohu Wang 2,  Chen Dong 5
Affiliations

Affiliations

  • 1 Institute for Immunology and School of Basic Medical Sciences, Tsinghua University, Beijing 100084, China; Tsinghua-Peking Center for Life Sciences, Beijing 100084, China.
  • 2 Institute for Immunology and School of Basic Medical Sciences, Tsinghua University, Beijing 100084, China.
  • 3 Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430207, China.
  • 4 MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
  • 5 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. Electronic address: dongchen@westlake.edu.cn.
PMID: 40222012 DOI: 10.1016/j.celrep.2025.115531
Abstract

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.

Keywords

CP: Immunology; HCoV-OC43; TLR2; alveolar macrophages; asymptomatic infection; neutrophil; severe pneumonia.

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