Legionella protection and vaccination mediated by Mucosal Associated Invariant T (MAIT) cells
Huimeng Wang, Criselle D’Souza, Xin Yi Lim, Lyudmila Kostenko, Troi J Pediongco, Sidonia BG Eckle, Bronwyn S Meehan, Nancy Wang, Shihan Li, Ligong Liu, Jeffrey YW Mak, David P Fairlie, Yoichiro Iwakura, Jennifer M Gunnersen, Andrew W Stent, Jamie Rossjohn, Glen P Westall, Lars KjerNielsen, Richard A Strugnell, James McCluskey, Alexandra J Corbett, and Timothy SC Hinks, Zhenjun Chen
Received: 19th October 17
Mucosal associated invariant T (MAIT) cells recognize conserved microbial metabolites from riboflavin synthesis. Striking evolutionary conservation and pulmonary abundance implicate them in antibacterial host defense, yet their roles in protection against clinically significant pathogens are unknown. Murine Legionella infection induced MR1-dependent MAIT cell activation and rapid pulmonary accumulation of MAIT cells associated with immune protection detectable in fully immunocompetent host animals. MAIT cell protection was more evident in mice lacking CD4+ cells, whilst profoundly immunodeficient RAG2-/-gC-/- mice were substantially rescued from uniformly lethal Legionella infection by adoptively-transferred MAIT cells. This protection was dependent on MR1, IFN-g and GM-CSF, but not IL-17, TNF-a or perforin. Protection was enhanced and observed earlier post-infection in mice that were Ag-primed to boost MAIT cells before infection. Our findings define a significant role for MAIT cells in protection against a major human pathogen and indicate a potential role for vaccination to enhance MAIT cell immunity.
Read in full at bioRxiv.
This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.