Figure 1.

Interactions among cells of the immune system in SARS-CoV-2-induced disease. SARS-CoV-2 antagonizes STAT1 phosphorylation, which is linked to the reduced immune activation in monocyte-derived dendritic cells (DCs). The impact of SARS-CoV-2 on DCs results in the production of autoantibodies against interferon (IFN)-1. Activation of CD8⁺ T cells is essential for virus clearance, and the activity of CD4⁺ T cells is important for the activation of CD8⁺ T cells and optimal antibody responses. IL-3 released from CD4⁺ and CD8⁺ T cells stimulates IFN-α, which is further linked to the higher fraction of plasmacytoid DCs (pDCs). The effector activity of T cells is suppressed by SARS-CoV-2 inducible effect on myeloid-derived suppressor cells (MDSCs) and further release of ILs 6 and 10 from the cells. IL-6 stimulatory effect on Notch4 expression from regulatory T cells (Tregs) contributed to severe lung inflammation via hampering release of amphiregulin. Granulocytic (G)-MDSCs also suppress the proliferation of T cells through the release of arginase-1 (ARG-1), which contributed to lyphocytopenia. ARG-1 activity and the resultant low L-arginine level contributed to platelet activation and thrombosis. In addition, MDSCs block IFN-γ production from T cells through releasing transforming growth factor (TGF)-β.