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.
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DOI：
10.1016/j.isci.2022.105319
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发表时间：
2022-11-18
期刊：
影响因子：
5.8
通讯作者：
Cheng, Liang
中科院分区：
文献类型：
--
作者：
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
SARS-CoV-2感染可导致重症COVID-19患者出现过度炎症等免疫反应失衡。在此，我们研究了COVID-19发病机制的免疫代谢调节机制。我们在单细胞水平上描述了COVID-19患者支气管肺泡灌洗液中免疫细胞，特别是巨噬细胞的代谢景观。我们发现，与健康对照相比，轻度COVID-19患者肺部巨噬细胞的大多数代谢过程上调，而重度COVID-19患者肺部巨噬细胞的大多数核心代谢途径（包括谷氨酸代谢、脂肪酸氧化、柠檬酸循环和氧化磷酸化）下调，少数途径（如糖酵解）上调。通过补充氨基酸、抑制糖酵解或刺激PPARγ来重新连接细胞代谢，可减少受SARS-CoV-2刺激的巨噬细胞的炎症。总之，本研究表明支气管肺泡巨噬细胞代谢失衡可能导致重症COVID-19患者的高炎症，并为通过免疫代谢调节治疗COVID-19提供了新的见解。代谢重编程不平衡可能导致肺巨噬细胞功能障碍重构代谢可减少SARS-CoV-2刺激下巨噬细胞的炎症免疫学;病毒学;生物信息学
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. 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
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