Siska, Peter J. and Decking, Sonja-Maria and Babl, Nathalie and Matos, Carina and Bruss, Christina and Singer, Katrin and Klitzke, Jana and Schoen, Marian and Simeth, Jakob and Koestler, Josef and Siegmund, Heiko and Ugele, Ines and Paulus, Michael and Dietl, Alexander and Kolodova, Kristina and Steines, Louisa and Freitag, Katharina and Peuker, Alice and Schoenhammer, Gabriele and Raithel, Johanna and Graf, Bernhard and Geismann, Florian and Lubnow, Matthias and Mack, Matthias and Hau, Peter and Bohr, Christopher and Burkhardt, Ralph and Gessner, Andre and Salzberger, Bernd and Wagner, Ralf and Hanses, Frank and Hitzenbichler, Florian and Heudobler, Daniel and Lueke, Florian and Pukrop, Tobias and Herr, Wolfgang and Wolff, Daniel and Spang, Rainer and Poeck, Hendrik and Hoffmann, Petra and Jantsch, Jonathan and Brochhausen, Christoph and Lunz, Dirk and Rehli, Michael and Kreutz, Marina and Renner, Kathrin (2021) Metabolic imbalance of T cells in COVID-19 is hallmarked by basigin and mitigated by dexamethasone. JOURNAL OF CLINICAL INVESTIGATION, 131 (22): e148225. ISSN 0021-9738, 1558-8238
Full text not available from this repository. (Request a copy)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
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