MAIT cells protect against pulmonary Legionella longbeachae infection

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 unkno...

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Main Authors: Wang, H, D'Souza, C, Lim, X, Kostenko, L, Pediongco, T, Eckle, S, Meehan, B, Shi, M, Wang, N, Li, S, Liu, L, Mak, J, Fairlie, D, Iwakura, Y, Gunnersen, J, Stent, A, Godfrey, D, Rossjohn, J, Westall, G, Kjer-Nielsen, L, Strugnell, R, McCluskey, J, Corbett, A, Hinks, T, Chen, Z
Format: Journal article
Published: Springer Nature 2018
_version_ 1797058263958683648
author Wang, H
D'Souza, C
Lim, X
Kostenko, L
Pediongco, T
Eckle, S
Meehan, B
Shi, M
Wang, N
Li, S
Liu, L
Mak, J
Fairlie, D
Iwakura, Y
Gunnersen, J
Stent, A
Godfrey, D
Rossjohn, J
Westall, G
Kjer-Nielsen, L
Strugnell, R
McCluskey, J
Corbett, A
Hinks, T
Chen, Z
author_facet Wang, H
D'Souza, C
Lim, X
Kostenko, L
Pediongco, T
Eckle, S
Meehan, B
Shi, M
Wang, N
Li, S
Liu, L
Mak, J
Fairlie, D
Iwakura, Y
Gunnersen, J
Stent, A
Godfrey, D
Rossjohn, J
Westall, G
Kjer-Nielsen, L
Strugnell, R
McCluskey, J
Corbett, A
Hinks, T
Chen, Z
author_sort Wang, H
collection OXFORD
description 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.
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spelling oxford-uuid:22fd61ef-b877-45d1-bc27-0735181da4252022-03-26T11:41:53ZMAIT cells protect against pulmonary Legionella longbeachae infectionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:22fd61ef-b877-45d1-bc27-0735181da425Symplectic Elements at OxfordSpringer Nature2018Wang, HD'Souza, CLim, XKostenko, LPediongco, TEckle, SMeehan, BShi, MWang, NLi, SLiu, LMak, JFairlie, DIwakura, YGunnersen, JStent, AGodfrey, DRossjohn, JWestall, GKjer-Nielsen, LStrugnell, RMcCluskey, JCorbett, AHinks, TChen, ZMucosal 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.
spellingShingle Wang, H
D'Souza, C
Lim, X
Kostenko, L
Pediongco, T
Eckle, S
Meehan, B
Shi, M
Wang, N
Li, S
Liu, L
Mak, J
Fairlie, D
Iwakura, Y
Gunnersen, J
Stent, A
Godfrey, D
Rossjohn, J
Westall, G
Kjer-Nielsen, L
Strugnell, R
McCluskey, J
Corbett, A
Hinks, T
Chen, Z
MAIT cells protect against pulmonary Legionella longbeachae infection
title MAIT cells protect against pulmonary Legionella longbeachae infection
title_full MAIT cells protect against pulmonary Legionella longbeachae infection
title_fullStr MAIT cells protect against pulmonary Legionella longbeachae infection
title_full_unstemmed MAIT cells protect against pulmonary Legionella longbeachae infection
title_short MAIT cells protect against pulmonary Legionella longbeachae infection
title_sort mait cells protect against pulmonary legionella longbeachae infection
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