Suppressive monocytes impair mait cells response via il-10 in patients with severe covid-19

Yang，Qianting1,2; Wen，Yanling1,2; Qi，Furong1,2; Gao，Xiang1,2; Chen，Weixin1,2; Xu，Gang1,2; Wei，Cailing1,2; Wang，Haiyan1,2; Tang，Xian1,2; Lin，Jingyan1,2; Zhao，Juanjuan1,2,3; Zhang，Mingxia1,2; Zhang，Shuye4; Zhang，Zheng1,2,3,5

2021-10-01

10.4049/jimmunol.2100228

JOURNAL OF IMMUNOLOGY   影响因子和分区

0022-1767

1550-6606

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/2 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/2 monocytes associated with functional impairment of MAIT cells through the IFN/IL-10 pathway.

SCI

英语

通讯

National Science Fund for Distinguished Young Scholars[82025022] ; Science and Technology Innovation Committee of Shenzhen Municipality[2020A1111350032] ; Central Charity Fund of Chinese Academy of Medical Science[2020-PT310-009] ; Shenzhen Bay Project["2020B1111340074","2020B1111340075"] ; Shenzhen Science and Technology Innovation Commission[JCYJ20190809170011461] ; China Postdoctoral Science Foundation["2020T130122ZX","2021M693357"] ; Guangdong Province Prevention["2020B1111340028","2020B11 11340032","2020B1111340040"]

Immunology

Immunology

WOS:000731192400007

AMER ASSOC IMMUNOLOGISTS

IMMUNOLOGY

2-s2.0-85115366029

Scopus

1.Institute for Hepatology,National Clinical Research Center for Infectious Disease,Shenzhen Third People's Hospital,Shenzhen,China
2.The Second Affiliated Hospital,School of Medicine,Southern University of Science and Technology,Shenzhen,China
3.Shenzhen Bay Laboratory,Shenzhen,China
4.Shanghai Public Health Clinical Center,Fudan University,Shanghai,China
5.Shenzhen Research Center for Communicable Disease Diagnosis and Treatment,Chinese Academy of Medical Science,Shenzhen,China

Yang，Qianting,Wen，Yanling,Qi，Furong,et al. Suppressive monocytes impair mait cells response via il-10 in patients with severe covid-19[J]. JOURNAL OF IMMUNOLOGY,2021,207(7):1848-1856.

Yang，Qianting.,Wen，Yanling.,Qi，Furong.,Gao，Xiang.,Chen，Weixin.,...&Zhang，Zheng.(2021).Suppressive monocytes impair mait cells response via il-10 in patients with severe covid-19.JOURNAL OF IMMUNOLOGY,207(7),1848-1856.

Yang，Qianting,et al."Suppressive monocytes impair mait cells response via il-10 in patients with severe covid-19".JOURNAL OF IMMUNOLOGY 207.7(2021):1848-1856.