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

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

Cell death & disease (2020-10-29)
Alessandra Sacchi, Germana Grassi, Veronica Bordoni, Patrizia Lorenzini, Eleonora Cimini, Rita Casetti, Eleonora Tartaglia, Luisa Marchioni, Nicola Petrosillo, Fabrizio Palmieri, Gianpiero D'Offizi, Stefania Notari, Massimo Tempestilli, Maria Rosaria Capobianchi, Emanuele Nicastri, Markus Maeurer, Alimuddin Zumla, Franco Locatelli, Andrea Antinori, Giuseppe Ippolito, Chiara Agrati
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.

MATERIALS
Product Number
Brand
Product Description

Roche
Phytohemagglutinin-M (PHA-M), from Phaseolus vulgaris