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Metabolic modeling of single bronchoalveolar macrophages reveals regulators of hyperinflammation in COVID-19.
Zhao, Qiuchen; Yu, Zhenyang; Zhang, Shengyuan; Shen, Xu-Rui; Yang, Hao; Xu, Yangyang; Liu, Yang; Yang, Lin; Zhang, Qing; Chen, Jiaqi; Lu, Mengmeng; Luo, Fei; Hu, Mingming; Gong, Yan; Xie, Conghua; Zhou, Peng; Wang, Li; Su, Lishan; Zhang, Zheng; Cheng, Liang.
  • Zhao Q; Department of Radiation and Medical Oncology, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.
  • Yu Z; 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.
  • Zhang S; School of Life Science, Wuhan University, Wuhan 430071, China.
  • Shen XR; Department of Radiation and Medical Oncology, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.
  • Yang H; 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.
  • Xu Y; 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.
  • Liu Y; 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.
  • Yang L; Department of Radiation and Medical Oncology, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.
  • Zhang Q; Department of Radiation and Medical Oncology, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.
  • Chen J; 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.
  • Lu M; Department of General Surgery, Xuzhou Mine Hospital, Xuzhou 221000, China.
  • Luo F; Cancer Institute, Xuzhou Medical University, Xuzhou 221000, China.
  • Hu M; School of Computer Sciences, Wuhan University, Wuhan 430071, China.
  • Gong Y; Department of Radiation and Medical Oncology, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.
  • Xie C; Department of Radiation and Medical Oncology, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.
  • Zhou P; 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.
  • Wang L; Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
  • Su L; Department of Radiation and Medical Oncology, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.
  • Zhang Z; Wuhan Research Center for Infectious Diseases and Cancer, Chinese Academy of Medical Sciences, Wuhan 430071, China.
  • Cheng L; 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.
iScience ; 25(11): 105319, 2022 Nov 18.
Article in English | MEDLINE | ID: covidwho-2061302
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Language: English Journal: IScience Year: 2022 Document Type: Article Affiliation country: J.isci.2022.105319

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Full text: Available Collection: International databases Database: MEDLINE Language: English Journal: IScience Year: 2022 Document Type: Article Affiliation country: J.isci.2022.105319