tetano
Editor, Senior Moderator
Front Immunol
. 2021 Jul 14;12:695972.
doi: 10.3389/fimmu.2021.695972. eCollection 2021.
Severe COVID-19 Is Characterized by an Impaired Type I Interferon Response and Elevated Levels of Arginase Producing Granulocytic Myeloid Derived Suppressor Cells
Matthew J Dean[SUP] 1 [/SUP], Juan B Ochoa[SUP] 2 [/SUP], Maria Dulfary Sanchez-Pino[SUP] 1 3 [/SUP], Jovanny Zabaleta[SUP] 1 4 [/SUP], Jone Garai[SUP] 1 [/SUP], Luis Del Valle[SUP] 1 5 [/SUP], Dorota Wyczechowska[SUP] 1 [/SUP], Lyndsey Buckner Baiamonte[SUP] 6 [/SUP], Phaethon Philbrook[SUP] 1 3 [/SUP], Rinku Majumder[SUP] 7 [/SUP], Richard S Vander Heide[SUP] 5 [/SUP], Logan Dunkenberger[SUP] 1 [/SUP], Ramesh Puttalingaiah Thylur[SUP] 1 [/SUP], Bobby Nossaman[SUP] 2 [/SUP], W Mark Roberts[SUP] 8 [/SUP], Andrew G Chapple[SUP] 1 9 [/SUP], Jiande Wu[SUP] 3 [/SUP], Chindo Hicks[SUP] 3 [/SUP], Jack Collins[SUP] 10 [/SUP], Brian Luke[SUP] 10 [/SUP], Randall Johnson[SUP] 10 [/SUP], Hari K Koul[SUP] 1 7 [/SUP], Chris A Rees[SUP] 11 [/SUP], Claudia R Morris[SUP] 12 [/SUP], Julia Garcia-Diaz[SUP] 6 [/SUP], Augusto C Ochoa[SUP] 1 4 [/SUP]
Affiliations
Abstract
COVID-19 ranges from asymptomatic in 35% of cases to severe in 20% of patients. Differences in the type and degree of inflammation appear to determine the severity of the disease. Recent reports show an increase in circulating monocytic-myeloid-derived suppressor cells (M-MDSC) in severe COVID 19 that deplete arginine but are not associated with respiratory complications. Our data shows that differences in the type, function and transcriptome of granulocytic-MDSC (G-MDSC) may in part explain the severity COVID-19, in particular the association with pulmonary complications. Large infiltrates by Arginase 1[SUP]+[/SUP] G-MDSC (Arg[SUP]+[/SUP]G-MDSC), expressing NOX-1 and NOX-2 (important for production of reactive oxygen species) were found in the lungs of patients who died from COVID-19 complications. Increased circulating Arg[SUP]+[/SUP]G-MDSC depleted arginine, which impaired T cell receptor and endothelial cell function. Transcriptomic signatures of G-MDSC from patients with different stages of COVID-19, revealed that asymptomatic patients had increased expression of pathways and genes associated with type I interferon (IFN), while patients with severe COVID-19 had increased expression of genes associated with arginase production, and granulocyte degranulation and function. These results suggest that asymptomatic patients develop a protective type I IFN response, while patients with severe COVID-19 have an increased inflammatory response that depletes arginine, impairs T cell and endothelial cell function, and causes extensive pulmonary damage. Therefore, inhibition of arginase-1 and/or replenishment of arginine may be important in preventing/treating severe COVID-19.
Keywords: COVID-19; G-MDSC; arginase; arginine; coronavirus; interferon; lung injury.
. 2021 Jul 14;12:695972.
doi: 10.3389/fimmu.2021.695972. eCollection 2021.
Severe COVID-19 Is Characterized by an Impaired Type I Interferon Response and Elevated Levels of Arginase Producing Granulocytic Myeloid Derived Suppressor Cells
Matthew J Dean[SUP] 1 [/SUP], Juan B Ochoa[SUP] 2 [/SUP], Maria Dulfary Sanchez-Pino[SUP] 1 3 [/SUP], Jovanny Zabaleta[SUP] 1 4 [/SUP], Jone Garai[SUP] 1 [/SUP], Luis Del Valle[SUP] 1 5 [/SUP], Dorota Wyczechowska[SUP] 1 [/SUP], Lyndsey Buckner Baiamonte[SUP] 6 [/SUP], Phaethon Philbrook[SUP] 1 3 [/SUP], Rinku Majumder[SUP] 7 [/SUP], Richard S Vander Heide[SUP] 5 [/SUP], Logan Dunkenberger[SUP] 1 [/SUP], Ramesh Puttalingaiah Thylur[SUP] 1 [/SUP], Bobby Nossaman[SUP] 2 [/SUP], W Mark Roberts[SUP] 8 [/SUP], Andrew G Chapple[SUP] 1 9 [/SUP], Jiande Wu[SUP] 3 [/SUP], Chindo Hicks[SUP] 3 [/SUP], Jack Collins[SUP] 10 [/SUP], Brian Luke[SUP] 10 [/SUP], Randall Johnson[SUP] 10 [/SUP], Hari K Koul[SUP] 1 7 [/SUP], Chris A Rees[SUP] 11 [/SUP], Claudia R Morris[SUP] 12 [/SUP], Julia Garcia-Diaz[SUP] 6 [/SUP], Augusto C Ochoa[SUP] 1 4 [/SUP]
Affiliations
- PMID: 34341659
- PMCID: PMC8324422
- DOI: 10.3389/fimmu.2021.695972
Abstract
COVID-19 ranges from asymptomatic in 35% of cases to severe in 20% of patients. Differences in the type and degree of inflammation appear to determine the severity of the disease. Recent reports show an increase in circulating monocytic-myeloid-derived suppressor cells (M-MDSC) in severe COVID 19 that deplete arginine but are not associated with respiratory complications. Our data shows that differences in the type, function and transcriptome of granulocytic-MDSC (G-MDSC) may in part explain the severity COVID-19, in particular the association with pulmonary complications. Large infiltrates by Arginase 1[SUP]+[/SUP] G-MDSC (Arg[SUP]+[/SUP]G-MDSC), expressing NOX-1 and NOX-2 (important for production of reactive oxygen species) were found in the lungs of patients who died from COVID-19 complications. Increased circulating Arg[SUP]+[/SUP]G-MDSC depleted arginine, which impaired T cell receptor and endothelial cell function. Transcriptomic signatures of G-MDSC from patients with different stages of COVID-19, revealed that asymptomatic patients had increased expression of pathways and genes associated with type I interferon (IFN), while patients with severe COVID-19 had increased expression of genes associated with arginase production, and granulocyte degranulation and function. These results suggest that asymptomatic patients develop a protective type I IFN response, while patients with severe COVID-19 have an increased inflammatory response that depletes arginine, impairs T cell and endothelial cell function, and causes extensive pulmonary damage. Therefore, inhibition of arginase-1 and/or replenishment of arginine may be important in preventing/treating severe COVID-19.
Keywords: COVID-19; G-MDSC; arginase; arginine; coronavirus; interferon; lung injury.