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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), 755-772.e5. 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.
FUNDING: This work was supported by NIH/NIAID (U01AI066569 and UM1AI104681), the Defense Advanced Projects Agency (DARPA; N66001-09-C-2082 and HR0011-17-2-0069), the Veterans Affairs Health System, and Virology Quality Assurance (VQA; 75N93019C00015). The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Institutes of Health. COVID-19 samples were processed under Biosafety level 2 (BSL-2) with aerosol management enhancement or BSL-3 in the Duke Regional Biocontainment Laboratory, which received partial support for construction from NIH/NIAID (UC6AI058607).
