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 Nussing; Sneha Sant; Zhongfang Wang; Criselle D'Souza; Xiaoxiao Jia; Catarina F Almeida; Lyudmila Kostenko; Sidonia BG Eckle; Bronwyn S Meehan; Axel Kallies; Dale I Godfrey; Patrick C Reading; Alexandra J Corbett; James McCluskey; Paul Klenerman; Katherine Kedzierska; Timothy SC Hinks

Journal article

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 Nussing, Sneha Sant, Zhongfang Wang, Criselle D'Souza, Xiaoxiao Jia, Catarina F Almeida, Lyudmila Kostenko, Sidonia BG Eckle, Bronwyn S Meehan, Axel Kallies, Dale I Godfrey, Patrick C Reading Show all

NATURE COMMUNICATIONS | NATURE PUBLISHING GROUP | Published : 2018

DOI: 10.1038/s41467-018-07207-9

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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-defic..

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University of Melbourne Researchers

Dale Godfrey Author Microbiology and Immunology

Alexandra Corbett Author Microbiology and Immunology

Zhongfang Wang Author Microbiology and Immunology

Huimeng Wang Author Microbiology and Immunology

Xiaoxiao Jia Author Microbiology and Immunology

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Grants

Awarded by Royal Society

Awarded by People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant

Awarded by National Health and Medical Research Council of Australia (NHMRC) Program

Awarded by NHMRC Senior Principal Research Fellowship

Awarded by Australian Research Council (ARC)

Awarded by Wellcome Trust

Funding Acknowledgements

B.v.W. was supported by the Royal Society (IE160540). The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant agreement number 608765. The content represents only the authors' views and not those of the European Commission. T.S.C.H. is supported by a Wellcome Trust Postdoctoral Research Fellowship (104553/z/14/z). The work was supported by the National Health and Medical Research Council of Australia (NHMRC) Program Grants 1113293, 1071916, 1016629 and 606788, and Project Grant 1120467. A.J.C. is supported by an ARC Future Fellowship. S.B.G.E. is supported by an ARC DECRA Fellowship. H.W. is supported by a Melbourne International Engagement Award (University of Melbourne). C.D'S. is supported by a Melbourne International Research Scholarship and a Melbourne International Fee Remission Scholarship (University of Melbourne). S.S. is a recipient of Victoria India Doctoral Scholarship and Melbourne International Fee Remission Scholarship, University of Melbourne. M.K. and S.N. are recipients of Melbourne International Research Scholarship and Melbourne International Fee Remission Scholarships. D.I.G. is supported by an NHMRC Senior Principal Research Fellowship (1117766) and by the Australian Research Council (ARC; CE140100011). K.K. is an NHMRC Senior Research Level B Fellow. P.K. was supported by an NIHR Senior Fellowship, Oxford Martin School (PK) and the Wellcome Trust (WT109965MA). A.K. was supported by a Sylvia and Charles Viertel fellowship. We are grateful to the Doherty Institute Flow Cytometry Facility and to Prof. Ian van Driel, Dr. Sammy Bedoui, Dr. Thomas Gebhardt and Dr. Julia Prier, for their kind provision of IL12-/-, IL15-/-, IL18-/- and IFN alpha R-/- mice, reagents, intellectual and technical expertise.