Naslov (eng)

Reduced expression of autophagy markers and expansion of myeloid- derived suppressor cells correlate with poor T cell response in severe COVID-19 patients

Autor

Tomić, Sergej
Mitrović, Nebojša
Bekić, Marina
Tomašević, Ratko
Mikić, Dragan
Stojanović, Dragoš
Čolić, Miodrag
Radojević, Dušan
Dinić, Miroslav
Gruden-Movsesijan, Alisa
Đokić, Jelena
Ilić, Nataša
Stevanović, Dejan

Opis (eng)

ABSTRACT Widespread coronavirus disease (COVID)-19 is causing pneumonia, respiratory and multiorgan failure in susceptible individuals. Dysregulated immune response marks severe COVID-19, but the immunological mechanisms driving COVID-19 pathogenesis are still largely unknown, which is hampering the development of efficient treatments. Here we analyzed ~140 parameters of cellular and humoral immune response in peripheral blood of 41 COVID-19 patients and 16 age/gender-matched healthy donors by flow-cytometry, quantitative PCR, western blot and ELISA, followed by integrated correlation analyses with ~30 common clinical and laboratory parameters. We found that lymphocytopenia in severe COVID-19 patients (n=20) strongly affects T, NK and NKT cells, but not B cells and antibody production. Unlike increased activation of ICOS-1+ CD4+ T cells in mild COVID-19 patients (n=21), T cells in severe patients showed impaired activation, low IFN-γ production and high functional exhaustion, which correlated with significantly down-regulated HLA-DR expression in monocytes, dendritic cells and B cells. The latter phenomenon was followed by lower interferon responsive factor (IRF)-8 and autophagy-related genes expressions, and the expansion of myeloid derived suppressor cells (MDSC). Intriguingly, PD-L1-, ILT-3-, and IDO-1-expressing monocytic MDSC were the dominant producers of IL-6 and IL-10, which correlated with the increased inflammation and accumulation of regulatory B and T cell subsets in severe COVID-19 patients. Overall, down-regulated IRF-8 and autophagy-related genes expression, and the expansion of MDSC subsets could play critical roles in dysregulating T cell response in COVID-19, which could have large implications in diagnostics and design of novel therapeutics for this disease.

Jezik

engleski

Datum

2021

Licenca

Ovo delo je licencirano pod uslovima licence
Creative Commons CC BY 4.0 - Creative Commons Autorstvo 4.0 International License.

http://creativecommons.org/licenses/by/4.0/legalcode

Predmet

COVID-19, autophagy, cytokines, myeloid-derived suppressor cells, regulatory lymphocytes

Deo kolekcije (1)

o:25140

Radovi Instituta za primenu nuklearne energije - INEP