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MAIT cells protect against pulmonary Legionella longbeachae infection

Wang, Huimeng, D'Souza, Criselle, Lim, Xin Yi, Kostenko, Lyudmila, Pediongco, Troi J., Eckle, Sidonia B. G., Meehan, Bronwyn S., Shi, Mai, Wang, Nancy, Li, Shihan, Liu, Ligong, Mak, Jeffrey Y. W., Fairlie, David P., Iwakura, Yoichiro, Gunnersen, Jennifer M., Stent, Andrew W., Godfrey, Dale I., Rossjohn, Jamie, Westall, Glen P., Kjer-Nielsen, Lars, Strugnell, Richard A., McCluskey, James, Corbett, Alexandra J., Hinks, Timothy S. C. and Chen, Zhenjun 2018. MAIT cells protect against pulmonary Legionella longbeachae infection. Nature Communications 9 (1) , 3350. 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 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Additional Information: This article is licensed under a Creative Commons Attribution 4.0 International License
Publisher: Nature Publishing Group: Nature Communications / Nature Publishing Group
ISSN: 2041-1723
Date of First Compliant Deposit: 5 September 2018
Date of Acceptance: 27 April 2018
Last Modified: 11 Jul 2019 13:52
URI: http://orca.cf.ac.uk/id/eprint/114627

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