Mucosal-associated invariant T (MAIT) cells mediate protective host responses in sepsis
- University of Utah, United States
Abstract
Sepsis is a systemic inflammatory response to infection and a leading cause of death. Mucosal-associated invariant T (MAIT) cells are innate-like T cells enriched in mucosal tissues that recognize bacterial ligands. We investigated MAIT cells during clinical and experimental sepsis, and their contribution to host responses. In experimental sepsis, MAIT-deficient mice had significantly increased mortality and bacterial load, and reduced tissue-specific cytokine responses. MAIT cells of WT mice expressed lower levels of IFN-γ and IL-17a during sepsis compared to sham surgery, changes not seen in non-MAIT T cells. MAIT cells of patients at sepsis presentation were significantly reduced in frequency compared to healthy donors, and were more activated, with decreased IFN-γ production, compared to both healthy donors and paired 90-day samples. Our data suggest that MAIT cells are highly activated and become dysfunctional during clinical sepsis, and contribute to tissue-specific cytokine responses that are protective against mortality during experimental sepsis.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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Funding
National Institute of Allergy and Infectious Diseases (AI130378)
- Daniel T Leung
National Heart, Lung, and Blood Institute (HL092161)
- Matthew T Rondina
National Institute on Aging (AG040631)
- Matthew T Rondina
National Institute on Aging (AG048022)
- Matthew T Rondina
National Center for Advancing Translational Sciences (TL1TR002540)
- Daniel Labuz
National Institute of General Medical Sciences (HG008962)
- Cole P Anderson
University of Utah (3i Initiative Seed Grant)
- J Scott Hale
- Matthew T Rondina
- Daniel T Leung
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All animals were maintained and experiments were performed in accordance with The University of Utah and Institutional Animal Care and Use Committee (IACUC) approved guidelines (protocol # 18-10012).
Human subjects: Each patient or a legally authorized representative provided written, informed consent. The University of Utah Institutional Review Board approved this study. (protocol #102638).
Copyright
© 2020, Trivedi et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Mucosal-associated invariant T (MAIT) cells mediate protective host responses in sepsis
eLife 9:e55615.
https://doi.org/10.7554/eLife.55615
