DataSheet_2_Reduced Expression of Autophagy Markers and Expansion of Myeloid-Derived Suppressor Cells Correlate With Poor T Cell Response in Severe COVID-19 Patients.pdf
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.
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References
- https://doi.org//10.1371/journal.pone.0234765
- https://doi.org//10.1016/j.cell.2020.02.052
- https://doi.org//10.1186/s40249-020-00662-x
- https://doi.org//10.1126/science.abb8925
- https://doi.org//10.1172/JCI137244
- https://doi.org//10.1038/ni.3123
- https://doi.org//10.1172/JCI138554
- https://doi.org//10.1038/s41423-020-0402-2
- https://doi.org//10.1016/j.cell.2020.05.015
- https://doi.org//10.1126/sciimmunol.abd2071
- https://doi.org//10.1126/science.abc8511
- https://doi.org//10.1038/s41586-020-2456-9
- https://doi.org//10.1016/j.cell.2020.02.058
- https://doi.org//10.1172/jci.insight.138999
- https://doi.org//10.1038/s41591-020-0901-9
- https://doi.org//10.1093/nsr/nwaa041
- https://doi.org//10.1016/j.chom.2020.04.009
- https://doi.org//10.18632/oncotarget.2368
- https://doi.org//10.3389/fimmu.2019.00475
- https://doi.org//10.1002/cyto.a.24009
- https://doi.org//10.1046/j.1365-2249.2001.01623.x
- https://doi.org//10.1182/blood-2011-12-401083
- https://doi.org//10.1016/j.molimm.2018.05.009
- https://doi.org//10.1016/j.biomaterials.2017.08.040
- https://doi.org//10.1038/cmi.2018.2
- https://doi.org//10.1038/ncomms7379
- https://doi.org//10.1007/s00262-015-1791-4
- https://doi.org//10.1016/j.lfs.2020.118097
- https://doi.org//10.1038/ncomms12150
- https://doi.org//10.1007/s00262-010-0855-8
- https://doi.org//10.2147/IJN.S183510
- https://doi.org//10.1158/0008-5472.CAN-09-3690
- https://doi.org//10.1038/nri.2017.1
- https://doi.org//10.1016/j.lfs.2020.117788
- https://doi.org//10.1007/s12020-020-02383-5
- https://doi.org//10.1016/S2213-8587(20)30268-0
- https://doi.org//10.1038/s41590-020-0762-x
- https://doi.org//10.1128/JVI.06075-11
- https://doi.org//10.1073/pnas.1502619112
- https://doi.org//10.1038/s41422-020-0305-x
- https://doi.org//10.3389/fncel.2020.00229
- https://doi.org//10.1016/j.autrev.2020.102554
- https://doi.org//10.1126/science.abc5902
- https://doi.org//10.1126/science.abd3871
- https://doi.org//10.3389/fimmu.2018.01618
- https://doi.org//10.1038/35051100
- https://doi.org//10.1038/s41577-020-0402-6
- https://doi.org//10.1007/s12250-020-00265-8
- https://doi.org//10.1128/JVI.01281-09
- https://doi.org//10.1038/ni0602-506
- https://doi.org//10.1126/science.1090148
- https://doi.org//10.1038/nature05969
- https://doi.org//10.1371/journal.pone.0192709
- https://doi.org//10.1101/2020.07.10.197343
- https://doi.org//10.1101/2020.05.13.20100925
- https://doi.org//10.1182/blood-2012-12-473413
- https://doi.org//10.1002/stem.2565
- https://doi.org//10.1038/sj.cr.7310018
- https://doi.org//10.1080/15548627.2015.1100356
- https://doi.org//10.1080/15548627.2018.1474314
- https://doi.org//10.1016/j.kint.2020.05.001
- https://doi.org//10.1158/0008-5472.CAN-13-3182
- https://doi.org//10.1016/j.cyto.2013.06.205
- https://doi.org//10.1002/jmv.25801
- https://doi.org//10.1038/s41418-020-0572-6
- https://doi.org//10.1158/2159-8290.CD-RW2013-214
- https://doi.org//10.1016/j.celrep.2020.108185
- https://doi.org//10.1158/2326-6066.CIR-16-0297
- https://doi.org//10.1016/j.arcmed.2020.04.019
- https://doi.org//10.3389/fimmu.2017.00093
- https://doi.org//10.1016/j.mehy.2020.109754
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Categories
- Transplantation Immunology
- Tumour Immunology
- Immunology not elsewhere classified
- Immunology
- Veterinary Immunology
- Animal Immunology
- Genetic Immunology
- Applied Immunology (incl. Antibody Engineering, Xenotransplantation and T-cell Therapies)
- Autoimmunity
- Cellular Immunology
- Humoural Immunology and Immunochemistry
- Immunogenetics (incl. Genetic Immunology)
- Innate Immunity