1. Immunology and Inflammation
  2. Microbiology and Infectious Disease
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Human MAIT cells respond to and suppress HIV-1

  1. Chansavath Phetsouphanh  Is a corresponding author
  2. Prabhjeet Phalora
  3. Carl-Philipp Hackstein
  4. John Thornhill
  5. Mee Ling Munier
  6. Jodi Meyerowitz
  7. Lyle Murray
  8. Cloete VanVuuren
  9. Dominique Goedhals
  10. Linnea Drexhage
  11. Rebecca A Russell
  12. Quentin J Sattentau
  13. Jeffrey YW MAK
  14. David P Fairlie
  15. Sarah Fidler
  16. Anthony Kelleher
  17. John Frater
  18. Paul Klenerman
  1. University of Oxford, United Kingdom
  2. Imperial College London, United Kingdom
  3. University of New South Wales, Australia
  4. Military Hospital, South Africa
  5. University of the Free State, South Africa
  6. The University of Queensland, Australia
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Cite this article as: eLife 2021;10:e50324 doi: 10.7554/eLife.50324

Abstract

Human MAIT cells sit at the interface between innate and adaptive immunity, are polyfunctional and are capable of killing pathogen infected cells via recognition of the Class IB molecule MR1. MAIT cells have recently been shown to possess an antiviral protective role in vivo and we therefore sought to explore this in relation to HIV-1 infection. There was marked activation of MAIT cells in vivo in HIV-1 infected individuals, which decreased following ART. Stimulation of THP1 monocytes with R5 tropic HIVBAL potently activated MAIT cells in vitro. This activation was dependent on IL-12 and IL-18 but was independent of the TCR. Upon activation, MAIT cells were able to up-regulate granzyme B, IFNg and HIV-1 restriction factors CCL3, 4 and 5. Restriction factors produced by MAIT cells inhibited HIV-1 infection of primary PBMCs and immortalized target cells in vitro. These data reveal MAIT cells to be an additional T cell population responding to HIV-1, with a potentially important role in controlling viral replication at mucosal sites.

Data availability

Raw data from main figures are provided as source data files.

Article and author information

Author details

  1. Chansavath Phetsouphanh

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    For correspondence
    c.phetsouphanh@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6617-5995
  2. Prabhjeet Phalora

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Carl-Philipp Hackstein

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. John Thornhill

    Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Mee Ling Munier

    The Kirby Institute, University of New South Wales, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  6. Jodi Meyerowitz

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Lyle Murray

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Cloete VanVuuren

    Military Hospital, Bloemfontein, South Africa
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9095-0039
  9. Dominique Goedhals

    Division of Virology, University of the Free State, Free State, South Africa
    Competing interests
    The authors declare that no competing interests exist.
  10. Linnea Drexhage

    Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  11. Rebecca A Russell

    Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  12. Quentin J Sattentau

    Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7170-1937
  13. Jeffrey YW MAK

    ARC Centre of Excellence in Advanced Molecular Imaging, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia
    Competing interests
    The authors declare that no competing interests exist.
  14. David P Fairlie

    ARC Centre of Excellence in Advanced Molecular Imaging, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia
    Competing interests
    The authors declare that no competing interests exist.
  15. Sarah Fidler

    Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  16. Anthony Kelleher

    The Kirby Institute, University of New South Wales, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  17. John Frater

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7163-7277
  18. Paul Klenerman

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4307-9161

Funding

Wellcome Trust (WT109965MA)

  • Paul Klenerman

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: The SPARTAC trial (EudraCT Number: 2004-000446-20) was approved by the following authorities: the Medicines and Healthcare products Regulatory Agency (UK), the Ministry of Health (Brazil), the Irish Medicines Board (Ireland), the Medicines Control Council (South Africa) and the Uganda National Council for Science and Technology (Uganda). It was also approved by the following ethics committees in the participating countries: the Central London Research Ethics Committee (UK), Hospital Universitário Clementino Fraga Filho Ethics in Research Committee (Brazil), the Clinical Research and Ethics Committee of Hospital Clinic in the province of Barcelona (Spain), the Adelaide and Meath Hospital Research Ethics Committee (Ireland), the University of Witwatersrand Human Research Ethics Committee, the University of Kwazulu-Natal Research Ethics Committee and the University of Cape Town Research Ethics Committee (South Africa), Uganda Virus Research Institute Science and ethics committee (Uganda), the Prince Charles Hospital Human Research Ethics Committee and St Vincent's Hospital Human Research Ethics Committee (Australia) and the National Institute for Infectious Diseases Lazzaro Spallanzani, Institute Hospital and the Medical Research Ethics Committee, and the ethical committee of the Central Foundation of San Raffaele, MonteTabor (Italy).Recruitment for and studies within the HEATHER cohort were approved by the West Midlands-South Birmingham Research Ethics Committee (reference 14/WM/1104). Recruitment of CHI participants were approved by The University of the Free State Ethics Committee (ETOVS 171/08). LTNPs recruitment was approved by The St Vincent's Human Research Ethics Committee (EC00140) approval number: HREC/12/SVH/298, SVH 12/217. PBMCs obtained from healthy donors were approved by the Sheffield Research Ethics Committee (reference 16/YH/0247). Participants were aged 18 years or older, all participants from each of the above mentioned cohorts gave informed and written consent for their participation in these studies.

Reviewing Editor

  1. Stipan Jonjic, University of Rijeka, Croatia

Publication history

  1. Received: July 18, 2019
  2. Accepted: December 23, 2021
  3. Accepted Manuscript published: December 24, 2021 (version 1)
  4. Version of Record published: January 11, 2022 (version 2)

Copyright

© 2021, Phetsouphanh 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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