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Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 J+Immunol 2021 ; 207 (7): 1848-1856 Nephropedia Template TP
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Suppressive Monocytes Impair MAIT Cells Response via IL-10 in Patients with Severe COVID-19 #MMPMID34452933
Yang Q; Wen Y; Qi F; Gao X; Chen W; Xu G; Wei C; Wang H; Tang X; Lin J; Zhao J; Zhang M; Zhang S; Zhang Z
J Immunol 2021[Oct]; 207 (7): 1848-1856 PMID34452933show ga
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-DR(low/-) 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-alpha pretreatment suppressed MAIT cells' response to E. coli by triggering high levels of IL-10 production by HLA-DR(low/-)-suppressive monocytes. Blocking IFN-alpha 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-DR(low/-) monocytes associated with functional impairment of MAIT cells through the IFN/IL-10 pathway.
|Adolescent[MESH]
|Adult[MESH]
|Asymptomatic Diseases[MESH]
|COVID-19/*immunology[MESH]
|Cells, Cultured[MESH]
|Child[MESH]
|Coinfection[MESH]
|Disease Progression[MESH]
|Escherichia coli Infections/*immunology[MESH]
|Escherichia coli/*physiology[MESH]
|Female[MESH]
|Humans[MESH]
|Immune Tolerance[MESH]
|Interleukin-10/*metabolism[MESH]
|Lymphocyte Activation[MESH]
|Male[MESH]
|Middle Aged[MESH]
|Monocytes/*immunology[MESH]
|Mucosal-Associated Invariant T Cells/*immunology[MESH]