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Mucosal-associated invariant T cell responses differ by sex in COVID-19
Yu, C., Littleton, S., Giroux, N. S., Mathew, R., Ding, S., Kalnitsky, J., Yang, Y., Petzold, E., Chung, H. A., Rivera, G. O., Rotstein, T., Xi, R., Ko, E. R., Tsalik, E. L., Sempowski, G. D., Denny, T. N., Burke, T. W., McClain, M. T., Woods, C. W., ... Saban, D. R. (2021). Mucosal-associated invariant T cell responses differ by sex in COVID-19. Med (New York, N.Y.), 2(6), 755-+. https://doi.org/10.1016/j.medj.2021.04.008
Background: Sexual dimorphisms in immune responses contribute to coronavirus disease 2019 (COVID-19) outcomes, but the mechanisms governing this disparity remain incompletely understood.Methods: We carried out sex-balanced sampling of peripheral blood mononuclear cells from hospitalized and non-hospitalized individuals with confirmed COVID-19, uninfected close contacts, and healthy control individuals for 36-color flow cytometry and single-cell RNA sequencing.Findings: 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 suggests that this reduction represented a major wave of MAIT cell extravasation during early infection in females. Moreover, MAIT cells from females possessed an immunologically active gene signature, whereas cells from males were pro-apoptotic.Conclusions: Our findings uncover a female-specific protective MAIT cell profile, potentially shedding light on reduced COVID-19 susceptibility in females.
