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

  • Yang Q
  • Wen Y
  • Qi F
  • et al.
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Abstract

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

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APA

Yang, Q., Wen, Y., Qi, F., Gao, X., Chen, W., Xu, G., … Zhang, Z. (2021). Suppressive Monocytes Impair MAIT Cells Response via IL-10 in Patients with Severe COVID-19. The Journal of Immunology, 207(7), 1848–1856. https://doi.org/10.4049/jimmunol.2100228

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