Suppressive Monocytes Impair MAIT Cells Response via IL-10 in Patients with Severe COVID-19.
J Immunol
; 207(7): 1848-1856, 2021 10 01.
Article
in English
| MEDLINE | ID: covidwho-1377034
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Monocytes
/
Interleukin-10
/
Escherichia coli
/
Escherichia coli Infections
/
Mucosal-Associated Invariant T Cells
/
SARS-CoV-2
/
COVID-19
Type of study:
Prognostic study
Limits:
Adolescent
/
Adult
/
Child
/
Female
/
Humans
/
Male
/
Middle aged
/
Young adult
Language:
English
Journal:
J Immunol
Year:
2021
Document Type:
Article
Affiliation country:
Jimmunol.2100228
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