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 and Zhenjun Chen
Additional contact information
Huimeng Wang: University of Melbourne
Criselle D’Souza: University of Melbourne
Xin Yi Lim: University of Melbourne
Lyudmila Kostenko: University of Melbourne
Troi J. Pediongco: University of Melbourne
Sidonia B. G. Eckle: University of Melbourne
Bronwyn S. Meehan: University of Melbourne
Mai Shi: University of Melbourne
Nancy Wang: University of Melbourne
Shihan Li: University of Melbourne
Ligong Liu: The University of Queensland
Jeffrey Y. W. Mak: The University of Queensland
David P. Fairlie: The University of Queensland
Yoichiro Iwakura: Tokyo University of Science
Jennifer M. Gunnersen: University of Melbourne
Andrew W. Stent: University of Melbourne
Dale I. Godfrey: University of Melbourne
Jamie Rossjohn: Monash University
Glen P. Westall: Alfred Hospital
Lars Kjer-Nielsen: University of Melbourne
Richard A. Strugnell: University of Melbourne
James McCluskey: University of Melbourne
Alexandra J. Corbett: University of Melbourne
Timothy S. C. Hinks: University of Melbourne
Zhenjun Chen: University of Melbourne

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-05202-8

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