MAIT cells protect against pulmonary Legionella longbeachae infection

Huimeng Wang; Criselle D'Souza; Xin Yi Lim; Lyudmila Kostenko; Troi J Pediongco; Sidonia B G Eckle; Bronwyn S Meehan; Mai Shi; Nancy Wang; Shihan Li; Ligong Liu; Jeffrey Y W Mak; David P Fairlie; Yoichiro Iwakura; Jennifer M Gunnersen; Andrew W Stent; Dale I Godfrey; Jamie Rossjohn; Glen P Westall; Lars Kjer-Nielsen; Richard A Strugnell; James McCluskey; Alexandra J Corbett; Timothy S C Hinks; Zhenjun Chen

doi:10.1038/s41467-018-05202-8

MAIT cells protect against pulmonary Legionella longbeachae infection

Nat Commun. 2018 Aug 22;9(1):3350. doi: 10.1038/s41467-018-05202-8.

Authors

Huimeng Wang¹, Criselle D'Souza^{1

2}, Xin Yi Lim¹, Lyudmila Kostenko¹, Troi J Pediongco¹, Sidonia B G Eckle¹, Bronwyn S Meehan¹, Mai Shi¹, Nancy Wang¹, Shihan Li^{1

3}, Ligong Liu^{4

5}, Jeffrey Y W Mak^{4

5}, David P Fairlie^{4

5}, Yoichiro Iwakura⁶, Jennifer M Gunnersen⁷, Andrew W Stent⁸, Dale I Godfrey^{1

3}, Jamie Rossjohn^{9

10

11}, Glen P Westall¹², Lars Kjer-Nielsen¹, Richard A Strugnell¹, James McCluskey¹³, Alexandra J Corbett¹, Timothy S C Hinks^{1

14}, Zhenjun Chen¹

Affiliations

¹ Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, 3010, Australia.
² Centre for Animal Biotechnology, Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Melbourne, VIC, 3010, Australia.
³ Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, VIC, 3010, Australia.
⁴ Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.
⁵ Australian Research Council Centre of Excellence in Advanced Molecular Imaging, The University of Queensland, Brisbane, QLD, 4072, Australia.
⁶ Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba-ken, 278-8510, Japan.
⁷ Anatomy and Neuroscience Department, University of Melbourne, Melbourne, VIC, 3000, Australia.
⁸ Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Melbourne, VIC, 3000, Australia.
⁹ Infection and Immunity Program and the Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia.
¹⁰ Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, VIC, 3800, Australia.
¹¹ Institute of Infection and Immunity, Cardiff University, School of Medicine, Heath Park, CF14 4XN, Wales, UK.
¹² Allergy Immunology and Respiratory Medicine, Alfred Hospital, Melbourne, VIC, 3004, Australia.
¹³ Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, 3010, Australia. jamesm1@unimelb.edu.au.
¹⁴ Respiratory Medicine Unit, Nuffield Department of Medicine Experimental Medicine and NIHR Oxford Biomedical Research Centre, University of Oxford, Oxfordshire, UK.

Abstract

Mucosal associated invariant T (MAIT) cells recognise conserved microbial metabolites from riboflavin synthesis. Striking evolutionary conservation and pulmonary abundance implicate them in antibacterial host defence, yet their functions in protection against clinically important pathogens are unknown. Here we show that mouse Legionella longbeachae infection induces MR1-dependent MAIT cell activation and rapid pulmonary accumulation of MAIT cells associated with immune protection detectable in immunocompetent host animals. MAIT cell protection is more evident in mice lacking CD4⁺ cells, and adoptive transfer of MAIT cells rescues immunodeficient Rag2^-/-γC^-/- mice from lethal Legionella infection. Protection is dependent on MR1, IFN-γ and GM-CSF, but not IL-17A, TNF or perforin, and enhanced protection is detected earlier after infection of mice antigen-primed to boost MAIT cell numbers before infection. Our findings define a function for MAIT cells in protection against a major human pathogen and indicate a potential role for vaccination to enhance MAIT cell immunity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
CD4-Positive T-Lymphocytes / metabolism
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism
Humans
Interleukin-17 / metabolism
Legionella longbeachae / immunology
Legionella longbeachae / pathogenicity*
Legionellosis / immunology
Legionellosis / microbiology
Lung / metabolism
Lung / microbiology*
Male
Mice
Mucosal-Associated Invariant T Cells / immunology*
Mucosal-Associated Invariant T Cells / metabolism
Perforin / metabolism

Substances

DNA-Binding Proteins
Interleukin-17
Rag2 protein, mouse
Perforin

Grants and funding

Wellcome Trust/United Kingdom