Single-Cell Transcriptomic Profiling of MAIT Cells in Patients With COVID-19

Abstract

BackgroundMucosal-associated invariant T (MAIT) cells are considered to participate of the host immune response against acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; however, single-cell transcriptomic profiling of MAIT cells in patients with COVID-19 remains unexplored.MethodsWe performed single-cell RNA sequencing analyses on peripheral MAIT cells from 13 patients with COVID-19 and 5 healthy donors. The transcriptional profiles of MAIT cells, together with assembled T-cell receptor sequences, were analyzed. Flow cytometry analysis was also performed to investigate the properties of MAIT cells.ResultsWe identified that differentially expressed genes (DEGs) of MAIT cells were involved in myeloid leukocyte activation and lymphocyte activation in patients with COVID-19. In addition, in MAIT cells from severe cases, more DEGs were enriched in adaptive cellular and humoral immune responses compared with those in moderate cases. Further analysis indicated that the increase of cell cytotoxicity (killing), chemotaxis, and apoptosis levels in MAIT cells were consistent with disease severity and displayed the highest levels in patients with severe disease. Interestingly, flow cytometry analysis showed that the frequencies of pyroptotic MAIT cells, but not the frequencies of apoptotic MAIT cells, were increased significantly in patients with COVID-19, suggesting pyroptosis is one of leading causes of MAIT cell deaths during SARS-CoV-2 infection. Importantly, there were more clonal expansions of MAIT cells in severe cases than in moderate cases.ConclusionsThe results of the present study suggest that MAIT cells are likely to be involved in the host immune response against SARS-CoV-2 infection. Simultaneously, the transcriptomic data from MAIT cells provides a deeper understanding of the immune pathogenesis of the disease.

Emerging Roles of Mucosal-Associated Invariant T Cells in Rheumatology

“…Homing of MAIT cells to inflamed tissues, as evidenced by high expression of chemokine receptors, and activation-induced cell death may contribute to the decrease in circulating MAIT cells. In patients with COVID-19, the frequency of pyroptotic MAIT cells rather than apoptotic MAIT cells is significantly increased, suggesting that activated MAIT cells may exhibit different forms of morbidity ( 61 ). Furthermore, a previous study has shown that the CD3 + MR1-tetramer + MAIT cell frequency is similar in HCs and patients with RA and that CD161 is reduced in early RA patients, indicating that the gating strategy of CD3 + CD161 + Vα7.2 + might be partially responsible for the reduction in MAIT cells ( 48 ).…”

Co-Regulation of Protein Coding Genes by Transcription Factor and Long Non-Coding RNA in SARS-CoV-2 Infected Cells: An In Silico Analysis

“…It has been demonstrated that host responses to SARS-CoV-2 are dependent on viral load and infection time course, with observed differences due to age and sex that may contribute to disease severity [13]. In severe COVID-19 patients, differentially expressed genes are enriched with adaptive cellular and humoral immune responses, cell cytotoxicity, chemotaxis, and apoptosis compared with those in moderate cases [24]. In summary, altered expression of genes might play important role in COVID-19 in IFN response, although remains debated.…”

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

“…Sc-RNA-seq analysis revealed a depletion of MAIT cells in patients with severe disease even if the number of clonotypes of MAIT cells was relatively high. Moreover, there were more large clonal expansions (clonal size > 10) in the severe cases than in the other conditions [50].…”

“…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.…”