Details

Autor(en) / Beteiligte

• Dean, Matthew J
• Ochoa, Juan B
• Sanchez-Pino, Maria Dulfary
• Zabaleta, Jovanny
• Garai, Jone
• Del Valle, Luis
• Wyczechowska, Dorota
• Baiamonte, Lyndsey Buckner
• Philbrook, Phaethon
• Majumder, Rinku
• Vander Heide, Richard S
• Dunkenberger, Logan
• Thylur, Ramesh Puttalingaiah
• Nossaman, Bobby
• Roberts, W Mark
• Chapple, Andrew G
• Wu, Jiande
• Hicks, Chindo
• Collins, Jack
• Luke, Brian
• Johnson, Randall
• Koul, Hari K
• Rees, Chris A
• Morris, Claudia R
• Garcia-Diaz, Julia
• Ochoa, Augusto C

Titel

Severe COVID-19 Is Characterized by an Impaired Type I Interferon Response and Elevated Levels of Arginase Producing Granulocytic Myeloid Derived Suppressor Cells

Ist Teil von

• Frontiers in immunology, 2021-07, Vol.12, p.695972-695972

Ort / Verlag

Switzerland: Frontiers Media S.A

Erscheinungsjahr

2021

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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 G-MDSC (Arg 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 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.