Journal article

MAIT cells protect against pulmonary Legionella longbeachae infection

Huimeng Wang, Criselle D'Souza, Xin Yi Lim, Lyudmila Kostenko, Troi J Pediongco, Sidonia BG Eckle, Bronwyn S Meehan, Mai Shi, Nancy Wang, Shihan Li, Ligong Liu, Jeffrey YW Mak, David P Fairlie, Yoichiro Iwakura, Jennifer M Gunnersen, Andrew W Stent, Dale I Godfrey, Jamie Rossjohn, Glen P Westall, Lars Kjer-Nielsen Show all

NATURE COMMUNICATIONS | NATURE RESEARCH | Published : 2018

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 infec..

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Grants

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


Awarded by ARC Centre of Excellence


Awarded by Wellcome Trust Postdoctoral Research Fellowship


Awarded by NHMRC Senior Principal Research Fellowship


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.