MAIT cells contribute to protection against lethal influenza infection in vivo

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 Jia, Catarina F. Almeida, Lyudmila Kostenko, Sidonia B. G. Eckle, Bronwyn S. Meehan, Axel Kallies, Dale I. Godfrey, Patrick C. Reading, Alexandra J. Corbett, James McCluskey, Paul Klenerman (), Katherine Kedzierska and Timothy S. C. Hinks
Additional contact information
Bonnie van Wilgenburg: The Peter Doherty Institute for Infection and Immunity, The University of Melbourne
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
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
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

Nature Communications, 2018, vol. 9, issue 1, 1-9

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-07207-9

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