Single-cell analysis reveals T cell dysfunction driven by macrophages and differential expression of transposable elements in severe COVID-19 patients
Airu Zhu,
Liang Zhou,
Zhao Chen,
Dongdong Liu,
Huijian Feng,
Baomei Cai,
Xinwen Chen,
Jincun Zhao,
Jingxian Zhao,
Jiekai Chen,
Manshu Li,
Jiangping He
Affiliations
Airu Zhu
State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China
Liang Zhou
Department of Critical Care Medicine, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital, Guangzhou Medical University, 151 Yanjiang Street West, Guangzhou, Guangdong, 510120, China
Zhao Chen
State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China
Dongdong Liu
Department of Critical Care Medicine, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital, Guangzhou Medical University, 151 Yanjiang Street West, Guangzhou, Guangdong, 510120, China
Huijian Feng
Center for Cell Lineage and Atlas, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China; Center for Cell Lineage and Atlas (CCLA), Bioland Laboratory, Guangzhou, China
Baomei Cai
Center for Cell Lineage and Atlas, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China; Center for Cell Lineage and Atlas (CCLA), Bioland Laboratory, Guangzhou, China
Xinwen Chen
Guangzhou National Laboratory, Guangzhou, China
Jincun Zhao
State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China; Guangzhou National Laboratory, Guangzhou, China
Jingxian Zhao
State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China; Guangzhou National Laboratory, Guangzhou, China
Jiekai Chen
Center for Cell Lineage and Atlas, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China; Center for Cell Lineage and Atlas (CCLA), Bioland Laboratory, Guangzhou, China
Manshu Li
Department of Critical Care Medicine, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital, Guangzhou Medical University, 151 Yanjiang Street West, Guangzhou, Guangdong, 510120, China; Corresponding author.
Jiangping He
Center for Cell Lineage and Atlas (CCLA), Bioland Laboratory, Guangzhou, China; Guangzhou National Laboratory, Guangzhou, China; Corresponding author. Center for Cell Lineage and Atlas (CCLA), Bioland Laboratory, Guangzhou, China.
The vastly spreading COVID-19 pneumonia is caused by SARS-CoV-2. Lymphopenia and cytokine levels are tightly associated with disease severity. However, virus-induced immune dysregulation at cellular and molecular levels remains largely undefined. Here, the leukocytes in the pleural effusion, sputum, and peripheral blood biopsies from severe and mild patients were analyzed at single-cell resolution. Drastic T cell hyperactivation accompanying elevated T cell exhaustion was observed, predominantly in pleural effusion. The mechanistic investigation identified a group of CD14+ monocytes and macrophages highly expressing CD163 and MRC1 in the biopsies from severe patients, suggesting M2 macrophage polarization. These M2-like cells exhibited up-regulated IL10, CCL18, APOE, CSF1 (M-CSF), and CCL2 signaling pathways. Further, cell type specific dysregulation of transposable elements was observed in Severe COVID-19 patients. Together, our results suggest that severe SARS-CoV-2 infection causes immune dysregulation by inducing M2 polarization and subsequent T cell exhaustion. This study improves our understanding of COVID-19 pathogenesis.
