期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 131, 期 22, 页码 -出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI148225
关键词
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资金
- Bavarian Ministry of Science and Arts
- Else Kroner Fresenius Foundation
- Bavarian Ministry of Science and Arts - Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [324392634-TRR 221]
- Marga and Walter Boll Foundation [220-05.01-15]
- BMBF [031A428A]
The study found that COVID-19 patients exhibited immunometabolic dysregulation, particularly in T cells, which showed increased ROS levels and metabolic quiescence. Treatment with dexamethasone could reduce ROS levels and improve gene expression profiles in T cells.
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
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