Early expansion of myeloid-derived suppressor cells inhibits SARS-CoV-2 specific T-cell response and may predict fatal COVID-19 outcome

The immunological mechanisms underlying the clinical presentation of SARS-CoV-2 infection and those influencing the disease outcome remain to be defined. Myeloid-derived suppressor cells (MDSC) have been described to be highly increased during COVID-19, however, their role remains elusive. We perfor...

Celý popis

Uloženo v:

Podrobná bibliografie
Vydáno v:	Cell death & disease Ročník 11; číslo 10; s. 921
Hlavní autoři:	Sacchi, Alessandra, Grassi, Germana, Bordoni, Veronica, Lorenzini, Patrizia, Cimini, Eleonora, Casetti, Rita, Tartaglia, Eleonora, Marchioni, Luisa, Petrosillo, Nicola, Palmieri, Fabrizio, D’Offizi, Gianpiero, Notari, Stefania, Tempestilli, Massimo, Capobianchi, Maria Rosaria, Nicastri, Emanuele, Maeurer, Markus, Zumla, Alimuddin, Locatelli, Franco, Antinori, Andrea, Ippolito, Giuseppe, Agrati, Chiara
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 27.10.2020 Springer Nature B.V
Témata:	13/21 38/77 692/420/254 692/699/255/2514 Aged Antibodies Area Under Curve Betacoronavirus - immunology Betacoronavirus - isolation & purification Betacoronavirus - metabolism Biochemistry Biomedical and Life Sciences Cell Biology Cell Culture Coronavirus Infections - immunology Coronavirus Infections - mortality Coronavirus Infections - pathology Coronavirus Infections - virology Coronaviruses COVID-19 Female Humans IL-1β Immunology Interferon-gamma - metabolism Interleukin 6 Interleukin 8 Interleukin-1beta - blood Interleukin-6 - blood Life Sciences Lymphocytes T Male Middle Aged Myeloid-Derived Suppressor Cells - cytology Myeloid-Derived Suppressor Cells - immunology Neutrophils - cytology Neutrophils - immunology Neutrophils - metabolism Nitric Oxide Synthase Type II - metabolism Nitric-oxide synthase Pandemics Peptides - immunology Peptides - metabolism Plasma levels Pneumonia, Viral - immunology Pneumonia, Viral - mortality Pneumonia, Viral - pathology Pneumonia, Viral - virology Proportional Hazards Models ROC Curve SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 Suppressor cells Survival Rate T-Lymphocytes - cytology T-Lymphocytes - immunology T-Lymphocytes - metabolism Transforming Growth Factor beta - blood Transforming Growth Factor beta - metabolism Tumor necrosis factor-α γ-Interferon
ISSN:	2041-4889, 2041-4889
On-line přístup:	Získat plný text
Tagy:	Přidat tag Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!

Popis
Shrnutí:	The immunological mechanisms underlying the clinical presentation of SARS-CoV-2 infection and those influencing the disease outcome remain to be defined. Myeloid-derived suppressor cells (MDSC) have been described to be highly increased during COVID-19, however, their role remains elusive. We performed an in depth analysis of MDSC in 128 SARS-CoV-2 infected patients. Polymorphonuclear (PMN)-MDSC expanded during COVID-19, in particular in patients who required intensive care treatments, and correlated with IL-1β, IL-6, IL-8, and TNF-α plasma levels. PMN-MDSC inhibited T-cells IFN-γ production upon SARS-CoV-2 peptides stimulation, through TGF-β- and iNOS-mediated mechanisms, possibly contrasting virus elimination. Accordingly, a multivariate regression analysis found a strong association between PMN-MDSC percentage and fatal outcome of the disease. The PMN-MDSC frequency was higher in non-survivors than survivors at the admission time, followed by a decreasing trend. Interestingly, this trend was associated with IL-6 increase in non-survivors but not in survivors. In conclusion, this study indicates PMN-MDSC as a novel factor in the pathogenesis of SARS-CoV2 infection, and open up to new therapeutic options.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-4889 2041-4889
DOI:	10.1038/s41419-020-03125-1