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  3. Metabolic modeling of single bronchoalveolar macrophages reveals regulators of hyperinflammation in COVID-19

Metabolic modeling of single bronchoalveolar macrophages reveals regulators of hyperinflammation in COVID-19

  • iScience. 2022 Oct 10;25(11):105319. doi: 10.1016/j.isci.2022.105319.
Qiuchen Zhao 1 2 3,  Zhenyang Yu 1 2,  Shengyuan Zhang 4,  Xu-Rui Shen 5,  Hao Yang 1,  Yangyang Xu 1,  Yang Liu 4,  Lin Yang 6,  Qing Zhang 7,  Jiaqi Chen 8,  Mengmeng Lu 1,  Fei Luo 1,  Mingming Hu 2,  Yan Gong 9,  Conghua Xie 1 10,  Peng Zhou 5,  Li Wang 2 11,  Lishan Su 12,  Zheng Zhang 4,  Liang Cheng 1 2 10
Affiliations

Affiliations

  • 1 Department of Radiation and Medical Oncology, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.
  • 2 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.
  • 3 School of Life Science, Wuhan University, Wuhan 430071, China.
  • 4 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.
  • 5 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.
  • 6 Department of General Surgery, Xuzhou Mine Hospital, Xuzhou 221000, China.
  • 7 Cancer Institute, Xuzhou Medical University, Xuzhou 221000, China.
  • 8 School of Computer Sciences, Wuhan University, Wuhan 430071, China.
  • 9 Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
  • 10 Wuhan Research Center for Infectious Diseases and Cancer, Chinese Academy of Medical Sciences, Wuhan 430071, China.
  • 11 Department of Cardiology, Institute of Myocardial Injury and Repair, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
  • 12 Division of Virology, Pathogenesis and Cancer, Institute of Human Virology and Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
PMID: 36246577 DOI: 10.1016/j.isci.2022.105319
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.

Keywords

Bioinformatics; Biological sciences; Immunology; Virology.

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