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

Satanay Hubrack,Patrick Tang,Mohammed Abu Khattab,Maryam Ali Al-Nesf,Christophe Raynaud,Nourhen Agrebi,Said Dermime,Michal Kulinski,Bernice Lo,Salma Taha,Maysaloun Merhi,Tayseer Ibrahim,Martin Steinhoff,Merlin Thomas

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.

Highlights

Mucosal-associated invariant T (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
MAIT cells were identified as CD161 + Vα7.2 + T cells (Fig. 1A), and their frequencies were quantified in Peripheral blood mononuclear cells (PBMCs) isolated from 21 healthy individuals and 36 SARS-CoV-2 positive patients (23 mildly affected and 13 severely affected)
Our results show a significant decrease in MAIT cell frequency in severely affected COVID-19 patients (Fig. 1B)

Summary

Introduction

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. A few studies have shown a similar activation of MAIT cells in response to severe acute respiratory coronavirus 2 (SARS-CoV-2) infection. 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). Mucosal-associated invariant T (MAIT) cells are a sub-population of innate T lymphocytes with effector-like properties[1] They are mainly found in the blood, lung, liver, and mucosa serving as sentinels against microbial and fungal infection[1,2]. MAIT cell activation correlates with disease severity in acute dengue infection[5], and the reconstitution of MAIT cell levels in peripheral blood was suggested to have a positive outcome in HIV patients[6]. One report associated the activation status of MAIT cells with disease severity and poor patient outcome[13], while another recent study described altered function of MAIT cells in COVID-19 patients, due to an imbalance in IFN-α and IL-1816

Methods

Results

Conclusion