Single-Cell RNA Sequencing Analysis of the Immunometabolic Rewiring and Immunopathogenesis of Coronavirus Disease 2019

Qi，Furong1,2; Zhang，Wenbo3; Huang，Jialu4; Fu，Lili5; Zhao，Jinfang5

2021-04-14

10.3389/fimmu.2021.651656

Frontiers in Immunology   影响因子和分区

1664-3224

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 (PKM, LDHA and PKM) and PPP-related genes (PGD and TKT) 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 (NSD1, KMT2E, and SETD2) and elevated transcription levels of genes involved in OXPHOS (ATP6V1B2, ATP5A1, ATP5E, and ATP5B), which may inhibit M2-like polarization. Plasma cells also expressed higher levels of the OXPHOS gene ATP13A3 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.

antibody secretion COVID-19 inflammation metabolic changes peripheral blood mononuclear cells

SCI

英语

第一

WOS:000644863200001

2-s2.0-85104991519

Scopus

1.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
2.Shenzhen Research Center for Communicable Disease Diagnosis and Treatment of Chinese Academy of Medical Science,Shenzhen,China
3.Trinity School of Durham and Chapel Hill,Durham,United States
4.Electronic and Computer Engineering,China North Vehicle Research Institute,Beijing,China
5.Center for Life Sciences,Tsinghua University,Beijing,China

Qi，Furong,Zhang，Wenbo,Huang，Jialu,et al. Single-Cell RNA Sequencing Analysis of the Immunometabolic Rewiring and Immunopathogenesis of Coronavirus Disease 2019[J]. Frontiers in Immunology,2021,12.

Qi，Furong,Zhang，Wenbo,Huang，Jialu,Fu，Lili,&Zhao，Jinfang.(2021).Single-Cell RNA Sequencing Analysis of the Immunometabolic Rewiring and Immunopathogenesis of Coronavirus Disease 2019.Frontiers in Immunology,12.

Qi，Furong,et al."Single-Cell RNA Sequencing Analysis of the Immunometabolic Rewiring and Immunopathogenesis of Coronavirus Disease 2019".Frontiers in Immunology 12(2021).