期刊
EMBO MOLECULAR MEDICINE
卷 12, 期 12, 页码 -出版社
WILEY
DOI: 10.15252/emmm.202013001
关键词
COVID-19; inhibitory checkpoints; mitochondria; monocytes; OXPHOS
资金
- Ministero della Salute [COVID-2020-12371808]
- Fondazione Cassa di Risparmio di Modena
- Glem Gas SpA (San Cesario, MO, Italy)
- Sanfelice 1893 Banca Popolare (San Felice sul Panaro, Modena, Italy)
- Rotary Club Distretto 2072 (Club in Modena)
- Rotary Club Distretto 2072 (Club in Modena L.A. Muratori)
- Rotary Club Distretto 2072 (Club in Carpi)
- Rotary Club Distretto 2072 (Club in Sassuolo)
- Rotary Club Distretto 2072 (Club in Castelvetro di Modena)
- C.O.F.I.M. SPA
- Biogas Europa Service Massimo Faccia
- Pierangelo Bertoli Fans Club
- Assicuratori Milanesi
- Gruppo BPER (Modena, Italy)
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-gamma 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据