Mucosal Associated Invariant T (MAIT) Cell Responses Differ by Sex in COVID-19

Abstract

Sexual dimorphisms in immune responses contribute to coronavirus disease 2019 (COVID-19) outcomes, yet the mechanisms governing this disparity remain incompletely understood. We carried out sex-balanced sampling of peripheral blood mononuclear cells from confirmed COVID-19 inpatients and outpatients, uninfected close contacts, and healthy controls for 36-color flow cytometry and single cell RNA-sequencing. Our results revealed a pronounced reduction of circulating mucosal associated invariant T (MAIT) cells in infected females. Integration of published COVID-19 airway tissue datasets implicate that this reduction represented a major wave of MAIT cell extravasation during early infection in females. Moreover, female MAIT cells possessed an immunologically active gene signature, whereas male counterparts were pro-apoptotic. Collectively, our findings uncover a female-specific protective MAIT profile, potentially shedding light on reduced COVID-19 susceptibility in females.

CD7-deleted hematopoietic stem cells can restore immunity after CAR T cell therapy

“…To further profile CD7 -T cells, we explored publicly available single-cell RNA sequencing (RNA-seq) data sets of healthy donor PBMCs (9)(10)(11). We found that CD7 transcript levels in T cells (defined as cells expressing TRAC and CD3E) in younger individuals (6-16 years) were significantly higher than older individuals (approximately 20-80 years), while T cells from supercentenarians (>110 years) had much lower expression of CD7 than the other 2 age cohorts (Supplemental Figure 1B).…”

Natural killer cells and unconventional T cells in COVID-19

“…Functionally, circulating MAIT cells are skewed towards a type 3 inflammatory state, and display impaired IFN-ɣ production potential and increased IL-17A release [ 9 •• , 10 •• ], similar to the Th17 skewing described for CD4 + T cells in severe COVID-19 [ 36 ]. Intriguingly, a recent study proposed that gender might have an impact on MAIT activation and lung infiltration [ 37 ], but further work is needed to further investigate such findings. MAIT cell depletion in peripheral blood is likely secondary to their migration to the inflamed lung, as supported by the increased MAIT cell frequencies in bronchoalveolar fluid (BALF), pleural fluid (PF), and endotracheal aspirates (ETA) of COVID-19 patients [ 9 •• , 10 •• , 32 ].…”

Comparing the age and sex trajectories of SARS-CoV-2 morbidity with other respiratory pathogens points to potential immune mechanisms

“…Greater male pathology seems associated with a failure to control the virus soon after infection (16,(25)(26)(27), while females may both detect (28,29) and respond (30,31) earlier. This female advantage may compound over age as a result of the age trajectories of particular immune effectors, e.g., Mucosal Associated Invariant T-cells which are an important line of defense in the lungs recruit more efficiently to airways (32), and deplete less rapidly with age in female blood. Conversely, female severe outcomes seem driven by over-responding immune systems, i.e., higher levels of innate immune cytokines were associated with worse disease progression in females, but not males (27).…”