Reduced Expression of Autophagy Markers and Expansion of Myeloid-Derived Suppressor Cells Correlate With Poor T Cell Response in Severe COVID-19 Patients
2021
Аутори
Tomić, SergejĐokić, Jelena
Stevanović, Dejan
Ilić, Nataša
Gruden-Movsesijan, Alisa
Dinić, Miroslav
Radojević, Dušan
Bekić, Marina
Mitrović, Nebojša
Tomasević, Ratko
Mikić, Dragan
Stojanović, Dragos
Čolić, Miodrag
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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 similar to 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 similar to 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-gamma production and high functional exhaus...tion, 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.
Кључне речи:
regulatory lymphocytes / myeloid-derived suppressor cells / cytokines / COVID-19 / autophagyИзвор:
Frontiers in Immunology, 2021, 12Издавач:
- Frontiers Media Sa, Lausanne
Финансирање / пројекти:
- Serbian Academy of Sciences and Arts
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200019 (Универзитет у Београду, Институт за примену нуклеарне енергије - ИНЕП) (RS-MESTD-inst-2020-200019)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200042 (Универзитет у Београду, Институт за молекуларну генетику и генетичко инжењерство) (RS-MESTD-inst-2020-200042)
- 451-03-921/2020-14/6
DOI: 10.3389/fimmu.2021.614599
ISSN: 1664-3224
PubMed: 33692788
WoS: 000626033700001
Scopus: 2-s2.0-85102247023
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Tomić, Sergej AU - Đokić, Jelena AU - Stevanović, Dejan AU - Ilić, Nataša AU - Gruden-Movsesijan, Alisa AU - Dinić, Miroslav AU - Radojević, Dušan AU - Bekić, Marina AU - Mitrović, Nebojša AU - Tomasević, Ratko AU - Mikić, Dragan AU - Stojanović, Dragos AU - Čolić, Miodrag PY - 2021 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1446 AB - 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 similar to 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 similar to 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-gamma 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. PB - Frontiers Media Sa, Lausanne T2 - Frontiers in Immunology T1 - Reduced Expression of Autophagy Markers and Expansion of Myeloid-Derived Suppressor Cells Correlate With Poor T Cell Response in Severe COVID-19 Patients VL - 12 DO - 10.3389/fimmu.2021.614599 ER -
@article{ author = "Tomić, Sergej and Đokić, Jelena and Stevanović, Dejan and Ilić, Nataša and Gruden-Movsesijan, Alisa and Dinić, Miroslav and Radojević, Dušan and Bekić, Marina and Mitrović, Nebojša and Tomasević, Ratko and Mikić, Dragan and Stojanović, Dragos and Čolić, Miodrag", year = "2021", 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 similar to 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 similar to 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-gamma 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.", publisher = "Frontiers Media Sa, Lausanne", journal = "Frontiers in Immunology", title = "Reduced Expression of Autophagy Markers and Expansion of Myeloid-Derived Suppressor Cells Correlate With Poor T Cell Response in Severe COVID-19 Patients", volume = "12", doi = "10.3389/fimmu.2021.614599" }
Tomić, S., Đokić, J., Stevanović, D., Ilić, N., Gruden-Movsesijan, A., Dinić, M., Radojević, D., Bekić, M., Mitrović, N., Tomasević, R., Mikić, D., Stojanović, D.,& Čolić, M.. (2021). Reduced Expression of Autophagy Markers and Expansion of Myeloid-Derived Suppressor Cells Correlate With Poor T Cell Response in Severe COVID-19 Patients. in Frontiers in Immunology Frontiers Media Sa, Lausanne., 12. https://doi.org/10.3389/fimmu.2021.614599
Tomić S, Đokić J, Stevanović D, Ilić N, Gruden-Movsesijan A, Dinić M, Radojević D, Bekić M, Mitrović N, Tomasević R, Mikić D, Stojanović D, Čolić M. Reduced Expression of Autophagy Markers and Expansion of Myeloid-Derived Suppressor Cells Correlate With Poor T Cell Response in Severe COVID-19 Patients. in Frontiers in Immunology. 2021;12. doi:10.3389/fimmu.2021.614599 .
Tomić, Sergej, Đokić, Jelena, Stevanović, Dejan, Ilić, Nataša, Gruden-Movsesijan, Alisa, Dinić, Miroslav, Radojević, Dušan, Bekić, Marina, Mitrović, Nebojša, Tomasević, Ratko, Mikić, Dragan, Stojanović, Dragos, Čolić, Miodrag, "Reduced Expression of Autophagy Markers and Expansion of Myeloid-Derived Suppressor Cells Correlate With Poor T Cell Response in Severe COVID-19 Patients" in Frontiers in Immunology, 12 (2021), https://doi.org/10.3389/fimmu.2021.614599 . .