SARS-CoV-2 Achieves Immune Escape by Destroying Mitochondrial Quality: Comprehensive Analysis of the Cellular Landscapes of Lung and Blood Specimens From Patients With COVID-19

作者全名："Duan, Chenyang; Ma, Ruiyan; Zeng, Xue; Chen, Bing; Hou, Dongyao; Liu, Ruixue; Li, Xuehan; Liu, Liangming; Li, Tao; Huang, He"

作者地址："[Duan, Chenyang; Zeng, Xue; Chen, Bing; Hou, Dongyao; Liu, Ruixue; Li, Xuehan; Huang, He] Chongqing Med Univ, Dept Anesthesiol, Affiliated Hosp 2, Chongqing, Peoples R China; [Ma, Ruiyan] Army Med Univ, Xinqiao Hosp, Dept Cardiovasc Surg, Chongqing, Peoples R China; [Liu, Liangming; Li, Tao] Army Med Univ, Daping Hosp, Dept Shock & Transfus, State Key Lab Trauma Burns & Combined Injury, Chongqing, Peoples R China"

通信作者："Duan, CY; Huang, H (通讯作者)，Chongqing Med Univ, Dept Anesthesiol, Affiliated Hosp 2, Chongqing, Peoples R China."

来源：FRONTIERS IN IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000827647000001

JCR分区：Q1

影响因子：7.3

年份：2022

卷号：13

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：COVID-19; mitochondrial quality; immune escape; inflammation; cytokine storm

摘要："Mitochondria get caught in the crossfire of coronavirus disease 2019 (COVID-19) and antiviral immunity. The mitochondria-mediated antiviral immunity represents the host's first line of defense against viral infection, and the mitochondria are important targets of COVID-19. However, the specific manifestations of mitochondrial damage in patients with COVID-19 have not been systematically clarified. This study comprehensively analyzed one single-cell RNA-sequencing dataset of lung tissue and two bulk RNA-sequencing datasets of blood from COVID-19 patients. We found significant changes in mitochondrion-related gene expression, mitochondrial functions, and related metabolic pathways in patients with COVID-19. SARS-CoV-2 first infected the host alveolar epithelial cells, which may have induced excessive mitochondrial fission, inhibited mitochondrial degradation, and destroyed the mitochondrial calcium uniporter (MCU). The type II alveolar epithelial cell count decreased and the transformation from type II to type I alveolar epithelial cells was blocked, which exacerbated viral immune escape and replication in COVID-19 patients. Subsequently, alveolar macrophages phagocytized the infected alveolar epithelial cells, which decreased mitochondrial respiratory capacity and activated the ROS-HIF1A pathway in macrophages, thereby aggravating the pro-inflammatory reaction in the lungs. Infected macrophages released large amounts of interferon into the blood, activating mitochondrial IFI27 expression and destroying energy metabolism in immune cells. The plasma differentiation of B cells and lung-blood interaction of regulatory T cells (Tregs) was exacerbated, resulting in a cytokine storm and excessive inflammation. Thus, our findings systematically explain immune escape and excessive inflammation seen during COVID-19 from the perspective of mitochondrial quality imbalance."

基金机构：China Postdoctoral Science Foundation [2021MD703924]; Chongqing Postdoctoral Innovative Talents Support Program [CQBX2021018]; Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University

基金资助正文："Funding This work was supported by the China Postdoctoral Science Foundation (2021MD703924), Chongqing Postdoctoral Innovative Talents Support Program (CQBX2021018) and Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University."