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Francisella tularensis induces Th1 like MAIT cells conferring protection against systemic and local infection

Author

Listed:
  • Zhe Zhao

    (Peter Doherty Institute for Infection and Immunity, The University of Melbourne)

  • Huimeng Wang

    (Peter Doherty Institute for Infection and Immunity, The University of Melbourne
    The First Affiliated Hospital of Guangzhou Medical University)

  • Mai Shi

    (Peter Doherty Institute for Infection and Immunity, The University of Melbourne
    Tsinghua University)

  • Tianyuan Zhu

    (Peter Doherty Institute for Infection and Immunity, The University of Melbourne
    Tsinghua University)

  • Troi Pediongco

    (Peter Doherty Institute for Infection and Immunity, The University of Melbourne)

  • Xin Yi Lim

    (Peter Doherty Institute for Infection and Immunity, The University of Melbourne)

  • Bronwyn S. Meehan

    (Peter Doherty Institute for Infection and Immunity, The University of Melbourne)

  • Adam G. Nelson

    (Peter Doherty Institute for Infection and Immunity, The University of Melbourne)

  • David P. Fairlie

    (Institute for Molecular Bioscience, The University of Queensland
    The University of Queensland)

  • Jeffrey Y. W. Mak

    (Institute for Molecular Bioscience, The University of Queensland
    The University of Queensland)

  • Sidonia B. G. Eckle

    (Peter Doherty Institute for Infection and Immunity, The University of Melbourne)

  • Marcela Moreira

    (Peter Doherty Institute for Infection and Immunity, The University of Melbourne)

  • Carolin Tumpach

    (Peter Doherty Institute for Infection and Immunity, The University of Melbourne)

  • Michael Bramhall

    (Peter Doherty Institute for Infection and Immunity, The University of Melbourne)

  • Cameron G. Williams

    (Peter Doherty Institute for Infection and Immunity, The University of Melbourne)

  • Hyun Jae Lee

    (Peter Doherty Institute for Infection and Immunity, The University of Melbourne)

  • Ashraful Haque

    (Peter Doherty Institute for Infection and Immunity, The University of Melbourne)

  • Maximilien Evrard

    (Peter Doherty Institute for Infection and Immunity, The University of Melbourne)

  • Jamie Rossjohn

    (Biomedicine Discovery Institute, Monash University
    Monash University
    Cardiff University School of Medicine)

  • James McCluskey

    (Peter Doherty Institute for Infection and Immunity, The University of Melbourne)

  • Alexandra J. Corbett

    (Peter Doherty Institute for Infection and Immunity, The University of Melbourne)

  • Zhenjun Chen

    (Peter Doherty Institute for Infection and Immunity, The University of Melbourne)

Abstract

Mucosal-associated Invariant T (MAIT) cells are recognized for their antibacterial functions. The protective capacity of MAIT cells has been demonstrated in murine models of local infection, including in the lungs. Here we show that during systemic infection of mice with Francisella tularensis live vaccine strain results in evident MAIT cell expansion in the liver, lungs, kidney and spleen and peripheral blood. The responding MAIT cells manifest a polarised Th1-like MAIT-1 phenotype, including transcription factor and cytokine profile, and confer a critical role in controlling bacterial load. Post resolution of the primary infection, the expanded MAIT cells form stable memory-like MAIT-1 cell populations, suggesting a basis for vaccination. Indeed, a systemic vaccination with synthetic antigen 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil in combination with CpG adjuvant similarly boosts MAIT cells, and results in enhanced protection against both systemic and local infections with different bacteria. Our study highlights the potential utility of targeting MAIT cells to combat a range of bacterial pathogens.

Suggested Citation

  • Zhe Zhao & Huimeng Wang & Mai Shi & Tianyuan Zhu & Troi Pediongco & Xin Yi Lim & Bronwyn S. Meehan & Adam G. Nelson & David P. Fairlie & Jeffrey Y. W. Mak & Sidonia B. G. Eckle & Marcela Moreira & Car, 2021. "Francisella tularensis induces Th1 like MAIT cells conferring protection against systemic and local infection," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24570-2
    DOI: 10.1038/s41467-021-24570-2
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    Cited by:

    1. Ann-Christin Gnirck & Marie-Sophie Philipp & Alex Waterhölter & Malte Wunderlich & Nikhat Shaikh & Virginia Adamiak & Lena Henneken & Tobias Kautz & Tingting Xiong & Daniela Klaus & Pascal Tomczyk & M, 2023. "Mucosal-associated invariant T cells contribute to suppression of inflammatory myeloid cells in immune-mediated kidney disease," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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