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Metabolic modeling of single bronchoalveolar macrophages reveals regulators of hyperinflammation in COVID-19
oleh: Qiuchen Zhao, Zhenyang Yu, Shengyuan Zhang, Xu-Rui Shen, Hao Yang, Yangyang Xu, Yang Liu, Lin Yang, Qing Zhang, Jiaqi Chen, Mengmeng Lu, Fei Luo, Mingming Hu, Yan Gong, Conghua Xie, Peng Zhou, Li Wang, Lishan Su, Zheng Zhang, Liang Cheng
Format: | Article |
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Diterbitkan: | Elsevier 2022-11-01 |
Deskripsi
Summary: 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.