학술논문
Metabolic imbalance of T cells in COVID-19 is hallmarked by basigin and mitigated by dexamethasone.
Document Type
Article
Author
Siska, Peter J.; Decking, Sonja-Maria; Babl, Nathalie; Matos, Carina; Bruss, Christina; Singer, Katrin; Klitzke, Jana; Schön, Marian; Simeth, Jakob; Köstler, Josef; Siegmund, Heiko; Ugele, Ines; Paulus, Michael; Dietl, Alexander; Kolodova, Kristina; Steines, Louisa; Freitag, Katharina; Peuker, Alice; Schönhammer, Gabriele; Raithel, Johanna
Source
Subject
Language
ISSN
0021-9738
Abstract
Metabolic pathways regulate immune responses and disrupted metabolism leads to immune dysfunction and disease. Coronavirus disease 2019 (COVID-19) is driven by imbalanced immune responses, yet the role of immunometabolism in COVID-19 pathogenesis remains unclear. By investigating 87 patients with confirmed SARS-CoV-2 infection, 6 critically ill non–COVID-19 patients, and 47 uninfected controls, we found an immunometabolic dysregulation in patients with progressed COVID-19. Specifically, T cells, monocytes, and granulocytes exhibited increased mitochondrial mass, yet only T cells accumulated intracellular reactive oxygen species (ROS), were metabolically quiescent, and showed a disrupted mitochondrial architecture. During recovery, T cell ROS decreased to match the uninfected controls. Transcriptionally, T cells from severe/ critical COVID-19 patients showed an induction of ROS-responsive genes as well as genes related to mitochondrial function and the basigin network. Basigin (CD147) ligands cyclophilin A and the SARS-CoV-2 spike protein triggered ROS production in T cells in vitro. In line with this, only PCR-positive patients showed increased ROS levels. Dexamethasone treatment resulted in a downregulation of ROS in vitro and T cells from dexamethasone-treated patients exhibited low ROS and basigin levels. This was reflected by changes in the transcriptional landscape. Our findings provide evidence of an immunometabolic dysregulation in COVID-19 that can be mitigated by dexamethasone treatment. [ABSTRACT FROM AUTHOR]