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.

Early expansion of myeloid-derived suppressor cells inhibits SARS-CoV-2 specific T-cell response and may predict fatal COVID-19 outcome / Sacchi, A.; Grassi, G.; Bordoni, V.; Lorenzini, P.; Cimini, E.; Casetti, R.; Tartaglia, E.; Marchioni, L.; Petrosillo, N.; Palmieri, F.; D'Offizi, G.; Notari, S.; Tempestilli, M.; Capobianchi, M. R.; Nicastri, E.; Maeurer, M.; Zumla, A.; Locatelli, F.; Antinori, A.; Ippolito, G.; Agrati, C.. - In: CELL DEATH & DISEASE. - ISSN 2041-4889. - 11:10(2020). [10.1038/s41419-020-03125-1]

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

Locatelli F.;
2020

Abstract

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.
2020
sars-cov-2; myeloid-derived suppressor cells; covid-19
01 Pubblicazione su rivista::01a Articolo in rivista
Early expansion of myeloid-derived suppressor cells inhibits SARS-CoV-2 specific T-cell response and may predict fatal COVID-19 outcome / Sacchi, A.; Grassi, G.; Bordoni, V.; Lorenzini, P.; Cimini, E.; Casetti, R.; Tartaglia, E.; Marchioni, L.; Petrosillo, N.; Palmieri, F.; D'Offizi, G.; Notari, S.; Tempestilli, M.; Capobianchi, M. R.; Nicastri, E.; Maeurer, M.; Zumla, A.; Locatelli, F.; Antinori, A.; Ippolito, G.; Agrati, C.. - In: CELL DEATH & DISEASE. - ISSN 2041-4889. - 11:10(2020). [10.1038/s41419-020-03125-1]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1480653
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