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

Zhao，Qiuchen1,2,11; Yu，Zhenyang1,2; Zhang，Shengyuan3; Shen，Xu Rui4; Yang，Hao1; Xu，Yangyang1; Liu，Yang3; Yang，Lin5; Zhang，Qing6; Chen，Jiaqi7; Lu，Mengmeng1; Luo，Fei1; Hu，Mingming2; Gong，Yan8; Xie，Conghua1,12; Zhou，Peng4; Wang，Li2,9; Su，Lishan10; Zhang，Zheng3; Cheng，Liang1,2,12

2022-11-18

10.1016/j.isci.2022.105319

iScience   Impact Factor & Quartile

2589-0042

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.

Bioinformatics Biological sciences Immunology Virology

English

Corresponding

Chinese Academy of Medical Sciences[2020-PT320-004];National Natural Science Foundation of China[82071784];Zhongnan Hospital of Wuhan University[ZNJC202007];

2-s2.0-85140413084

Scopus

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.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
4.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
5.Department of General Surgery,Xuzhou Mine Hospital,Xuzhou,221000,China
6.Cancer Institute,Xuzhou Medical University,Xuzhou,221000,China
7.School of Computer Sciences,Wuhan University,Wuhan,430071,China
8.Department of Biological Repositories,Zhongnan Hospital of Wuhan University,Wuhan,430071,China
9.Department of Cardiology,Institute of Myocardial Injury and Repair,Zhongnan Hospital of Wuhan University,Wuhan,430071,China
10.Division of Virology,Pathogenesis and Cancer,Institute of Human Virology and Department of Pharmacology,University of Maryland School of Medicine,Baltimore,21201,United States
11.School of Life Science,Wuhan University,Wuhan,430071,China
12.Wuhan Research Center for Infectious Diseases and Cancer,Chinese Academy of Medical Sciences,Wuhan,430071,China

Zhao，Qiuchen,Yu，Zhenyang,Zhang，Shengyuan,et al. Metabolic modeling of single bronchoalveolar macrophages reveals regulators of hyperinflammation in COVID-19[J]. iScience,2022,25(11).

Zhao，Qiuchen.,Yu，Zhenyang.,Zhang，Shengyuan.,Shen，Xu Rui.,Yang，Hao.,...&Cheng，Liang.(2022).Metabolic modeling of single bronchoalveolar macrophages reveals regulators of hyperinflammation in COVID-19.iScience,25(11).

Zhao，Qiuchen,et al."Metabolic modeling of single bronchoalveolar macrophages reveals regulators of hyperinflammation in COVID-19".iScience 25.11(2022).