RT Journal Article
SR Electronic
T1 <em>Legionella</em> protection and vaccination mediated by Mucosal Associated Invariant T (MAIT) cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 231472
DO 10.1101/231472
A1 Huimeng Wang
A1 Criselle D’Souza
A1 Xin Yi Lim
A1 Lyudmila Kostenko
A1 Troi J Pediongco
A1 Sidonia BG Eckle
A1 Bronwyn S Meehan
A1 Nancy Wang
A1 Shihan Li
A1 Ligong Liu
A1 Jeffrey YW Mak
A1 David P Fairlie
A1 Yoichiro Iwakura
A1 Jennifer M Gunnersen
A1 Andrew W Stent
A1 Jamie Rossjohn
A1 Glen P Westall
A1 Lars Kjer-Nielsen
A1 Richard A Strugnell
A1 James McCluskey
A1 Alexandra J Corbett
A1 Timothy SC Hinks
A1 Zhenjun Chen
YR 2017
UL http://biorxiv.org/content/early/2017/12/09/231472.abstract
AB 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−/−γC−/− mice were substantially rescued from uniformly lethal Legionella infection by adoptively-transferred MAIT cells. This protection was dependent on MR1, IFN-γ and GM-CSF, but not IL-17, TNF-α 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.