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

• Published in: iScience Vol. 25; no. 11; p. 105319
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.11.2022; Elsevier
• Subjects: Bioinformatics; Biological sciences; Immunology; Virology; Biological sciences; Immunology; Bioinformatics; Virology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2022.105319

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. [Display omitted] •Dysregulated metabolic activities of lung immune cells in severe COVID-19•Unbalanced metabolic reprogramming may lead to dysfunction of lung macrophages•Remodeling metabolism reduces inflammation in macrophages stimulated with SARS-CoV-2 Biological sciences; Immunology; Virology; Bioinformatics