Altered bioenergetics and mitochondrial dysfunction of monocytes in patients with COVID-19 pneumonia.
In patients infected by SARS-CoV-2 who experience an exaggerated inflammation leading to pneumonia, monocytes likely play a major role but have received poor attention. Thus, we analyzed peripheral blood monocytes from patients with COVID-19 pneumonia and found that these cells show signs of altered bioenergetics and mitochondrial dysfunction, had a reduced basal and maximal respiration, reduced spare respiratory capacity and decreased proton leak. Basal extracellular acidification rate was also diminished, suggesting reduced capability to perform aerobic glycolysis. Although COVID-19 monocytes had a reduced ability to perform oxidative burst, they were still capable of producing TNF and IFN-g,in vitro. A significantly high amount of monocytes had depolarized mitochondria and abnormal mitochondrial ultrastructure. A redistribution of monocyte subsets, with a significant expansion of intermediate/pro-inflammatory cells, and high amounts of immature monocytes were found, along with a concomitant compression of classical monocytes, and an increased expression of inhibitory checkpoints like PD-1/PD-L1. High plasma levels of several inflammatory cytokines and chemokines, including GM-CSF, IL-18, CCL2, CXCL10 and osteopontin, finally confirm the importance of monocytes in COVID-19 immunopathogenesis.
|Authors:||Gibellini L, De Biasi S, Paolini A, Borella R, Boraldi F, Mattioli M, Lo Tartaro D, Fidanza L, Caro-Maldonado A, Meschiari M, Iadisernia V, Bacca E, Riva G, Cicchetti L, Quaglino D, Guaraldi G, Busani S, Girardis M, Mussini C, Cossarizza A,|
|Journal:||EMBO Mol Med; 2020 Oct 19 13001. doi:10.15252/emmm.202013001|
|PubMed:||PMID: 33078545 (Go to PubMed)|