MAIT cells protect against pulmonary Legionella longbeachae infection

H Wang; C D’Souza; XY Lim; L Kostenko; TJ Pediongco; SBG Eckle; BS Meehan; M Shi; N Wang; S Li; L Liu; JYW Mak; DP Fairlie; Y Iwakura; JM Gunnersen; AW Stent; DI Godfrey; J Rossjohn; GP Westall; L Kjer-Nielsen; RA Strugnell; J McCluskey; AJ Corbett; TSC Hinks; Z Chen

Journal article

MAIT cells protect against pulmonary Legionella longbeachae infection

H Wang, C D’Souza, XY Lim, L Kostenko, TJ Pediongco, SBG Eckle, BS Meehan, M Shi, N Wang, S Li, L Liu, JYW Mak, DP Fairlie, Y Iwakura, JM Gunnersen, AW Stent, DI Godfrey, J Rossjohn, GP Westall, L Kjer-Nielsen Show all

Nature Communications | NATURE RESEARCH | Published : 2018

DOI: 10.1038/s41467-018-05202-8

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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 Legionellalongbeachae 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 infect..

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University of Melbourne Researchers

Sidonia Eckle Author

Bronwyn Meehan Author

Nancy Wang Author

Shihan Li Author

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Awarded by University of Melbourne

Funding Acknowledgements

This research was supported by the National Health and Medical Research Council of Australia (NHMRC) Program Grants 1113293, 1016629 and 606788, a Project Grant 1120467, an ARC Centre of Excellence grant CE140100011, as well as a Merieux Research Grant. T.S.C.H. was supported by a Wellcome Trust Postdoctoral Research Fellowship (104553/z/14/z). A.J.C. was supported by an ARC Future Fellowship. S.B.G.E. was supported by an ARC DECRA Fellowship. D.I.G. is supported by an NHMRC Senior Principal Research Fellowship (1117766). J.R. was supported by an Australian ARC Laureate Fellowship. D.P.F. was supported by an NHMRC Senior Principal Research 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). We thank Dr Wei-Jen Chua and Prof Ted Hansen for their kind provision of 8F2.F9 and 26.5 mAbs, and Professor David Jackson for Pam2Cys. We are grateful to Professor Francis Carbone for critical review of the manuscript.