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.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Shubhanshi Trivedi

    Internal Medicine (Infectious Diseases), University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Daniel Labuz

    Internal Medicine (Infectious Diseases), Pathology (Microbiology & Immunology), University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Cole P Anderson

    Department of Oncological Sciences; Molecular Medicine Program, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Claudia V Araujo

    Molecular Medicine Program, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Antoinette Blair

    Molecular Medicine Program, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Elizabeth A Middleton

    Molecular Medicine Program, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Owen Jensen

    Internal Medicine (Infectious Diseases), University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Alexander Tran

    Pathology, Div of Microbiology & Immunology, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Matthew A Mulvey

    Pathology, Div of Microbiology & Immunology, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Robert A Campbell

    Molecular Medicine Program, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. J Scott Hale

    Pathology, Div of Microbiology & Immunology, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Matthew T Rondina

    Pathology, Div of Microbiology & Immunology, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Daniel T Leung

    Internal Medicine (Infectious Diseases), University of Utah, Salt Lake City, United States
    For correspondence
    daniel.leung@utah.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8401-0801

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).

Reviewing Editor

  1. Nicola L Harris, Monash University, Australia

Publication history

  1. Received: January 30, 2020
  2. Accepted: November 9, 2020
  3. Accepted Manuscript published: November 9, 2020 (version 1)
  4. Version of Record published: November 20, 2020 (version 2)

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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  1. Shubhanshi Trivedi
  2. Daniel Labuz
  3. Cole P Anderson
  4. Claudia V Araujo
  5. Antoinette Blair
  6. Elizabeth A Middleton
  7. Owen Jensen
  8. Alexander Tran
  9. Matthew A Mulvey
  10. Robert A Campbell
  11. J Scott Hale
  12. Matthew T Rondina
  13. Daniel T Leung
(2020)
Mucosal-associated invariant T (MAIT) cells mediate protective host responses in sepsis
eLife 9:e55615.
https://doi.org/10.7554/eLife.55615

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