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

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.

Comprehensive Analysis of the ILCs and Unconventional T Cells in Virus Infection: Profiling and Dynamics Associated with COVID-19 Disease for a Future Monitoring System and Therapeutic Opportunities

“…In convalescent patients, MAIT cell frequency did not significantly increase. COVID-19 patients with mild symptoms showed a lower percentage [43,51,52] or a slightly higher one [48], or much more than in severe [40,46,49,53]. This data correlated with the low percentage of CCR6+ CCR7+ MAIT, suggesting a migration into inflamed tissues and/or activation-induced cell death.…”

“…In particular, CD69 was slightly lower in mild patients in percentage and MFI [48], while CD69 on MAIT cells of dead patients was higher than in patients who survived [40]. Interestingly, CD69 expression on MAIT positively correlated with the level of plasmatic IL-18 that was significantly higher in the plasma of long-term ICU patients with fatal COVID-19 [39,53] compared to plasma from patients hospitalized in an ICU or IDU [53].…”

“…Complex analyses were performed on blood by Flow cytometry (7/11 papers) and Sc-RNA-seq (8/11 papers) and on serum analyzed by Luminex or ELISA. Flow cytometry analysis showed that reduction of MAIT cells was significant in severe COVID-19 patients compared to healthy controls [39,40,43,46,[48][49][50][51][52][53] and compared to HCs or infected patients. In convalescent patients, MAIT cell frequency did not significantly increase.…”

“…When MAIT cells were stimulated with IL-12/IL-18 [48,52], there was a decrease in IL-17A and TNF-α compared to healthy controls and an increase in IFN-γ production [43,53], even though this finding was not the same for Hubrack et al [48]. Upon in vitro stimulation with Iono/PMA, MAIT from mild patients lowered IFN-γ production and increased GzB compared to HCs [53], while MAIT from severe patients increased IFN-γ, GzB and IL-17 (Figure 1B).…”

“…In contrast, CD69 expression increased more in infiltrating Unconventional T cells [39,48]. Indeed, the correlation between CD69 expression of MAIT cells and CXCR3 expression was frequently evaluated [40,53].…”