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MAIT cells contribute to protection against lethal influenza infection in vivo

Author

Listed:
  • Bonnie van Wilgenburg

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

  • Liyen Loh

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

  • Zhenjun Chen

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

  • Troi J. Pediongco

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

  • Huimeng Wang

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

  • Mai Shi

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

  • Zhe Zhao

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

  • Marios Koutsakos

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

  • Simone Nüssing

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

  • Sneha Sant

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

  • Zhongfang Wang

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

  • Criselle D’Souza

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

  • Xiaoxiao Jia

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

  • Catarina F. Almeida

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

  • Lyudmila Kostenko

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

  • Sidonia B. G. Eckle

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

  • Bronwyn S. Meehan

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

  • Axel Kallies

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

  • Dale I. Godfrey

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

  • Patrick C. Reading

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

  • Alexandra J. Corbett

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

  • James McCluskey

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

  • Paul Klenerman

    (University of Oxford)

  • Katherine Kedzierska

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

  • Timothy S. C. Hinks

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

Abstract

Mucosal associated invariant T (MAIT) cells are evolutionarily-conserved, innate-like lymphocytes which are abundant in human lungs and can contribute to protection against pulmonary bacterial infection. MAIT cells are also activated during human viral infections, yet it remains unknown whether MAIT cells play a significant protective or even detrimental role during viral infections in vivo. Using murine experimental challenge with two strains of influenza A virus, we show that MAIT cells accumulate and are activated early in infection, with upregulation of CD25, CD69 and Granzyme B, peaking at 5 days post-infection. Activation is modulated via cytokines independently of MR1. MAIT cell-deficient MR1−/− mice show enhanced weight loss and mortality to severe (H1N1) influenza. This is ameliorated by prior adoptive transfer of pulmonary MAIT cells in both immunocompetent and immunodeficient RAG2−/−γC−/− mice. Thus, MAIT cells contribute to protection during respiratory viral infections, and constitute a potential target for therapeutic manipulation.

Suggested Citation

  • Bonnie van Wilgenburg & Liyen Loh & Zhenjun Chen & Troi J. Pediongco & Huimeng Wang & Mai Shi & Zhe Zhao & Marios Koutsakos & Simone Nüssing & Sneha Sant & Zhongfang Wang & Criselle D’Souza & Xiaoxiao, 2018. "MAIT cells contribute to protection against lethal influenza infection in vivo," Nature Communications, Nature, vol. 9(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07207-9
    DOI: 10.1038/s41467-018-07207-9
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    Cited by:

    1. Mark Walkenhorst & Jana K. Sonner & Nina Meurs & Jan Broder Engler & Simone Bauer & Ingo Winschel & Marcel S. Woo & Lukas Raich & Iris Winkler & Vanessa Vieira & Lisa Unger & Gabriela Salinas & Olivie, 2024. "Protective effect of TCR-mediated MAIT cell activation during experimental autoimmune encephalomyelitis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. 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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