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...

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Bibliographic Details
Published in:Cell death & disease Vol. 11; no. 10; p. 921
Main Authors: 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
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 27.10.2020
Springer Nature B.V
Subjects:
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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
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Summary: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.
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ISSN:2041-4889
2041-4889
DOI:10.1038/s41419-020-03125-1