Suppressive Monocytes Impair MAIT Cells Response via IL-10 in Patients with Severe COVID-19

Abstract Immune cell responses are strikingly altered in patients with severe coronavirus disease 2019 (COVID-19), but the immunoregulatory process these individuals is not fully understood. In this study, 23 mild and 22 COVID-19 6 asymptomatic carriers of were enrolled, along 44 healthy controls (HC). Peripheral immune cells HC comprehensively profiled using mass cytometry. We found that COVID-19, number HLA-DRlow/? monocytes was significantly increased, mucosal-associated invariant T (MAIT) greatly reduced. MAIT highly activated functionally impaired response to Escherichia coli IL-12/IL-18 stimulation especially those microbial coinfection. Single-cell transcriptome analysis revealed IFN-stimulated genes upregulated peripheral from COVID-19. IFN-? pretreatment suppressed cells’ E. by triggering high levels IL-10 production HLA-DRlow/?–suppressive monocytes. Blocking or receptors rescued function Moreover, plasma inhibited HLA-DR expression through IL-10. These data indicate a unique pattern dysregulation which characterized enrichment suppressive associated functional impairment IFN/IL-10 pathway.