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体外白细胞介素 7 治疗部分挽救了 SARS-CoV-2 感染引起的 MAIT 细胞功能障碍。

In vitro Interleukin-7 treatment partially rescues MAIT cell dysfunction caused by SARS-CoV-2 infection.

机构信息

Department of Human Genetics, Research Branch, Sidra Medicine, 26999, Doha, Qatar.

Allergy and Clinical Immunology Section, Hamad Medical Corporation, 3050, Doha, Qatar.

出版信息

Sci Rep. 2021 Jul 8;11(1):14090. doi: 10.1038/s41598-021-93536-7.

Abstract

MAIT cells have been shown to be activated upon several viral infections in a TCR-independent manner by responding to inflammatory cytokines secreted by antigen-presenting cells. Recently, a few studies have shown a similar activation of MAIT cells in response to severe acute respiratory coronavirus 2 (SARS-CoV-2) infection. In this study, we investigate the effect of SARS-CoV-2 infection on the frequency and phenotype of MAIT cells by flow cytometry, and we test in vitro stimulation conditions on the capacity to enhance or rescue the antiviral function of MAIT cells from patients with coronavirus disease 2019 (COVID-19). Our study, in agreement with recently published studies, confirmed the decline in MAIT cell frequency of hospitalized donors in comparison to healthy donors. MAIT cells of COVID-19 patients also had lower expression levels of TNF-alpha, perforin and granzyme B upon stimulation with IL-12 + IL-18. 24 h' incubation with IL-7 successfully restored perforin expression levels in COVID-19 patients. Combined, our findings support the growing evidence that SARS-CoV-2 is dysregulating MAIT cells and that IL-7 treatment might improve their function, rendering them more effective in protecting the body against the virus.

摘要

MAIT 细胞在受到几种病毒感染时,可通过对抗原呈递细胞分泌的炎症细胞因子作出反应,以非 TCR 依赖性的方式被激活。最近,有几项研究表明,MAIT 细胞在严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)感染时也会发生类似的激活。在这项研究中,我们通过流式细胞术研究了 SARS-CoV-2 感染对 MAIT 细胞频率和表型的影响,并测试了体外刺激条件对从 2019 冠状病毒病(COVID-19)患者中增强或恢复 MAIT 细胞抗病毒功能的能力。我们的研究与最近发表的研究一致,证实了与健康供体相比,住院供体 MAIT 细胞频率下降。COVID-19 患者的 MAIT 细胞在受到 IL-12+IL-18 刺激时,TNF-α、穿孔素和颗粒酶 B 的表达水平也较低。用 IL-7 孵育 24 小时成功恢复了 COVID-19 患者穿孔素的表达水平。综上所述,我们的研究结果支持越来越多的证据表明,SARS-CoV-2 使 MAIT 细胞失调,而 IL-7 治疗可能改善其功能,使它们更有效地保护机体免受病毒侵害。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/812c/8266862/d3e13b7997b8/41598_2021_93536_Fig1_HTML.jpg

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