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

Yu, C.; Littleton, S.; Giroux, N.; Mathew, R.; Ding, S.; Kalnitsky, J.; Petzold, E.; Chung, H.; Palomino, G. r.; Rotstein, T.; Xi, R.; Ko, E. R.; Tsalik, E. L.; sempowski, g.; Denny, T. N.; Burke, T. W.; McClain, M. T.; Woods, C. W.; Shen, X.; Saban, D. R.

doi:10.1101/2020.12.01.407148

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bioRxiv · 10.1101/2020.12.01.407148

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

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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.

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Yu, C., Littleton, S., Giroux, N., Mathew, R., Ding, S., Kalnitsky, J., Petzold, E., Chung, H., Palomino, G. r., Rotstein, T., Xi, R., Ko, E. R., Tsalik, E. L., sempowski, g., Denny, T. N., Burke, T. W., McClain, M. T., Woods, C. W., Shen, X., Saban, D. R.. 2020-12-01. Mucosal Associated Invariant T (MAIT) Cell Responses Differ by Sex in COVID-19. https://doi.org/10.1101/2020.12.01.407148

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