iScience (Nov 2022)
Metabolic modeling of single bronchoalveolar macrophages reveals regulators of hyperinflammation in COVID-19
- Qiuchen Zhao,
- Zhenyang Yu,
- Shengyuan Zhang,
- Xu-Rui Shen,
- Hao Yang,
- Yangyang Xu,
- Yang Liu,
- Lin Yang,
- Qing Zhang,
- Jiaqi Chen,
- Mengmeng Lu,
- Fei Luo,
- Mingming Hu,
- Yan Gong,
- Conghua Xie,
- Peng Zhou,
- Li Wang,
- Lishan Su,
- Zheng Zhang,
- Liang Cheng
Affiliations
- Qiuchen Zhao
- Department of Radiation and Medical Oncology, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China; Frontier Science Center for Immunology and Metabolism, Department of Pulmonary and Critical Care Medicine, Zhongnan Hospital of Wuhan University, State Key Laboratory of Virology, Wuhan University, Wuhan 430071, China; School of Life Science, Wuhan University, Wuhan 430071, China
- Zhenyang Yu
- Department of Radiation and Medical Oncology, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China; Frontier Science Center for Immunology and Metabolism, Department of Pulmonary and Critical Care Medicine, Zhongnan Hospital of Wuhan University, State Key Laboratory of Virology, Wuhan University, Wuhan 430071, China
- Shengyuan Zhang
- Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, the Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen 518112, China
- Xu-Rui Shen
- CAS Key Laboratory of Special Pathogens and State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China
- Hao Yang
- Department of Radiation and Medical Oncology, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China
- Yangyang Xu
- Department of Radiation and Medical Oncology, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China
- Yang Liu
- Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, the Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen 518112, China
- Lin Yang
- Department of General Surgery, Xuzhou Mine Hospital, Xuzhou 221000, China
- Qing Zhang
- Cancer Institute, Xuzhou Medical University, Xuzhou 221000, China
- Jiaqi Chen
- School of Computer Sciences, Wuhan University, Wuhan 430071, China
- Mengmeng Lu
- Department of Radiation and Medical Oncology, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China
- Fei Luo
- Department of Radiation and Medical Oncology, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China
- Mingming Hu
- Frontier Science Center for Immunology and Metabolism, Department of Pulmonary and Critical Care Medicine, Zhongnan Hospital of Wuhan University, State Key Laboratory of Virology, Wuhan University, Wuhan 430071, China
- Yan Gong
- Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
- Conghua Xie
- Department of Radiation and Medical Oncology, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China; Wuhan Research Center for Infectious Diseases and Cancer, Chinese Academy of Medical Sciences, Wuhan 430071, China
- Peng Zhou
- CAS Key Laboratory of Special Pathogens and State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China
- Li Wang
- Frontier Science Center for Immunology and Metabolism, Department of Pulmonary and Critical Care Medicine, Zhongnan Hospital of Wuhan University, State Key Laboratory of Virology, Wuhan University, Wuhan 430071, China; Department of Cardiology, Institute of Myocardial Injury and Repair, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Corresponding author
- Lishan Su
- Division of Virology, Pathogenesis and Cancer, Institute of Human Virology and Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Corresponding author
- Zheng Zhang
- Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, the Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen 518112, China; Corresponding author
- Liang Cheng
- Department of Radiation and Medical Oncology, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China; Frontier Science Center for Immunology and Metabolism, Department of Pulmonary and Critical Care Medicine, Zhongnan Hospital of Wuhan University, State Key Laboratory of Virology, Wuhan University, Wuhan 430071, China; Wuhan Research Center for Infectious Diseases and Cancer, Chinese Academy of Medical Sciences, Wuhan 430071, China; Corresponding author
- Journal volume & issue
-
Vol. 25,
no. 11
p. 105319
Abstract
Summary: SARS-CoV-2 infection induces imbalanced immune response such as hyperinflammation in patients with severe COVID-19. Here, we studied the immunometabolic regulatory mechanisms for the pathogenesis of COVID-19. We depicted the metabolic landscape of immune cells, especially macrophages, from bronchoalveolar lavage fluid of patients with COVID-19 at single-cell level. We found that most metabolic processes were upregulated in macrophages from lungs of patients with mild COVID-19 compared to cells from healthy controls, whereas macrophages from severe COVID-19 showed downregulation of most of the core metabolic pathways including glutamate metabolism, fatty acid oxidation, citrate cycle, and oxidative phosphorylation, and upregulation of a few pathways such as glycolysis. Rewiring cellular metabolism by amino acid supplementation, glycolysis inhibition, or PPARγ stimulation reduces inflammation in macrophages stimulated with SARS-CoV-2. Altogether, this study demonstrates that metabolic imbalance of bronchoalveolar macrophages may contribute to hyperinflammation in patients with severe COVID-19 and provides insights into treating COVID-19 by immunometabolic modulation.
