Mucosal-associated invariant T cell responses differ by sex in COVID-19.

Journal Article (Journal Article)

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).

Full Text

Duke Authors

Cited Authors

  • Yu, C; Littleton, S; Giroux, NS; Mathew, R; Ding, S; Kalnitsky, J; Yang, Y; Petzold, E; Chung, HA; Rivera, GO; Rotstein, T; Xi, R; Ko, ER; Tsalik, EL; Sempowski, GD; Denny, TN; Burke, TW; McClain, MT; Woods, CW; Shen, X; Saban, DR

Published Date

  • June 11, 2021

Published In

Volume / Issue

  • 2 / 6

Start / End Page

  • 755 - 772.e5

PubMed ID

  • 33870241

Pubmed Central ID

  • PMC8043578

Electronic International Standard Serial Number (EISSN)

  • 2666-6340

Digital Object Identifier (DOI)

  • 10.1016/j.medj.2021.04.008


  • eng

Conference Location

  • United States