Mucosal-associated invariant T cell responses differ by sex in COVID-19.
Chen Yu, Sejiro Littleton, Nicholas S Giroux, Rose Mathew, Shengli Ding, Joan Kalnitsky, Yuchen Yang, Elizabeth Petzold, Hong A Chung, Grecia O Rivera, Tomer Rotstein, Rui Xi, Emily R Ko, Ephraim L Tsalik, Gregory D Sempowski, Thomas N Denny, Thomas W Burke, Micah T McClain, Christopher W Woods, Xiling Shen, Daniel R Saban
Author Information
Chen Yu: Department of Ophthalmology, Duke University School of Medicine, Durham, NC 27710, USA.
Sejiro Littleton: Department of Ophthalmology, Duke University School of Medicine, Durham, NC 27710, USA.
Nicholas S Giroux: Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27710, USA.
Rose Mathew: Department of Ophthalmology, Duke University School of Medicine, Durham, NC 27710, USA.
Shengli Ding: Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27710, USA.
Joan Kalnitsky: Department of Ophthalmology, Duke University School of Medicine, Durham, NC 27710, USA.
Yuchen Yang: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Elizabeth Petzold: Center for Applied Genomics and Precision Medicine, Duke University, Durham, NC 27710, USA.
Hong A Chung: Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27710, USA.
Grecia O Rivera: Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27710, USA.
Tomer Rotstein: Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27710, USA.
Rui Xi: Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27710, USA.
Emily R Ko: Center for Applied Genomics and Precision Medicine, Duke University, Durham, NC 27710, USA.
Ephraim L Tsalik: Center for Applied Genomics and Precision Medicine, Duke University, Durham, NC 27710, USA.
Gregory D Sempowski: Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA.
Thomas N Denny: Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA.
Thomas W Burke: Center for Applied Genomics and Precision Medicine, Duke University, Durham, NC 27710, USA.
Micah T McClain: Center for Applied Genomics and Precision Medicine, Duke University, Durham, NC 27710, USA.
Christopher W Woods: Center for Applied Genomics and Precision Medicine, Duke University, Durham, NC 27710, USA.
Xiling Shen: Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27710, USA.
Daniel R Saban: Department of Ophthalmology, Duke University School of Medicine, Durham, NC 27710, USA.
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).
