Qi Furong, Zhang Wenbo, Huang Jialu, Fu Lili, Zhao Jinfang
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, China.
Shenzhen Research Center for Communicable Disease Diagnosis and Treatment of Chinese Academy of Medical Science, Shenzhen, China.
Front Immunol. 2021 Apr 14;12:651656. doi: 10.3389/fimmu.2021.651656. eCollection 2021.
Although immune dysfunction is a key feature of coronavirus disease 2019 (COVID-19), the metabolism-related mechanisms remain elusive. Here, by reanalyzing single-cell RNA sequencing data, we delineated metabolic remodeling in peripheral blood mononuclear cells (PBMCs) to elucidate the metabolic mechanisms that may lead to the progression of severe COVID-19. After scoring the metabolism-related biological processes and signaling pathways, we found that mono-CD14 cells expressed higher levels of glycolysis-related genes ( and ) and PPPrelated genes ( and ) in severe patients than in mild patients. These genes may contribute to the hyperinflammation in mono-CD14 cells of patients with severe COVID-19. The mono-CD16 cell population in COVID-19 patients showed reduced transcription levels of genes related to lysine degradation (, and ) and elevated transcription levels of genes involved in OXPHOS (, , , and ), which may inhibit M2-like polarization. Plasma cells also expressed higher levels of the OXPHOS gene in COVID-19 patients, which was positively associated with antibody secretion and survival of PCs. Moreover, enhanced glycolysis or OXPHOS was positively associated with the differentiation of memory B cells into plasmablasts or plasma cells. This study comprehensively investigated the metabolic features of peripheral immune cells and revealed that metabolic changes exacerbated inflammation in monocytes and promoted antibody secretion and cell survival in PCs in COVID-19 patients, especially those with severe disease.
尽管免疫功能障碍是2019冠状病毒病（COVID-19）的一个关键特征，但与代谢相关的机制仍不清楚。在此，通过重新分析单细胞RNA测序数据，我们描绘了外周血单核细胞（PBMC）中的代谢重塑，以阐明可能导致重症COVID-19进展的代谢机制。在对与代谢相关的生物学过程和信号通路进行评分后，我们发现，与轻症患者相比，重症患者的单核CD14细胞中糖酵解相关基因（ 和 ）和磷酸戊糖途径（PPP）相关基因（ 和 ）表达水平更高。这些基因可能导致重症COVID-19患者单核CD14细胞中的炎症反应加剧。COVID-19患者的单核CD16细胞群体中，赖氨酸降解相关基因（ 、 和 ）的转录水平降低，而参与氧化磷酸化（OXPHOS）的基因（ 、 、 和 ）的转录水平升高，这可能会抑制M2样极化。浆细胞在COVID-19患者中也表达更高水平的OXPHOS基因 ，这与浆细胞的抗体分泌和存活呈正相关。此外，糖酵解或OXPHOS增强与记忆B细胞分化为成浆细胞或浆细胞呈正相关。本研究全面调查了外周免疫细胞的代谢特征，发现代谢变化加剧了COVID-19患者尤其是重症患者单核细胞中的炎症反应，并促进了浆细胞中的抗体分泌和细胞存活。
