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
  • 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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