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 & 5 others Richard A. Strugnell, James McCluskey, Alexandra J. Corbett, Timothy S.C. Hinks, Zhenjun Chen

Research output: Contribution to journalArticleResearchpeer-review

29 Citations (Scopus)

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 Legionellalongbeachae 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.

Original languageEnglish
Article number3350
Number of pages15
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Dec 2018

Cite this

Wang, H., D’Souza, C., Lim, X. Y., Kostenko, L., Pediongco, T. J., Eckle, S. B. G., ... Chen, Z. (2018). MAIT cells protect against pulmonary Legionella longbeachae infection. Nature Communications, 9(1), [3350]. https://doi.org/10.1038/s41467-018-05202-8
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. ; Chen, Zhenjun. / MAIT cells protect against pulmonary Legionella longbeachae infection. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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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 Legionellalongbeachae 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.",
author = "Huimeng Wang and Criselle D’Souza and Lim, {Xin Yi} and Lyudmila Kostenko and Pediongco, {Troi J.} and Eckle, {Sidonia B.G.} and Meehan, {Bronwyn S.} and Mai Shi and Nancy Wang and Shihan Li and Ligong Liu and Mak, {Jeffrey Y.W.} and Fairlie, {David P.} and Yoichiro Iwakura and Gunnersen, {Jennifer M.} and Stent, {Andrew W.} and Godfrey, {Dale I.} and Jamie Rossjohn and Westall, {Glen P.} and Lars Kjer-Nielsen and Strugnell, {Richard A.} and James McCluskey and Corbett, {Alexandra J.} and Hinks, {Timothy S.C.} and Zhenjun Chen",
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Wang, H, D’Souza, C, Lim, XY, Kostenko, L, Pediongco, TJ, Eckle, SBG, Meehan, BS, Shi, M, Wang, N, Li, S, Liu, L, Mak, JYW, Fairlie, DP, Iwakura, Y, Gunnersen, JM, Stent, AW, Godfrey, DI, Rossjohn, J, Westall, GP, Kjer-Nielsen, L, Strugnell, RA, McCluskey, J, Corbett, AJ, Hinks, TSC & Chen, Z 2018, 'MAIT cells protect against pulmonary Legionella longbeachae infection', Nature Communications, vol. 9, no. 1, 3350. https://doi.org/10.1038/s41467-018-05202-8

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.; Chen, Zhenjun.

In: Nature Communications, Vol. 9, No. 1, 3350, 01.12.2018.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Wang, Huimeng

AU - D’Souza, Criselle

AU - Lim, Xin Yi

AU - Kostenko, Lyudmila

AU - Pediongco, Troi J.

AU - Eckle, Sidonia B.G.

AU - Meehan, Bronwyn S.

AU - Shi, Mai

AU - Wang, Nancy

AU - Li, Shihan

AU - Liu, Ligong

AU - Mak, Jeffrey Y.W.

AU - Fairlie, David P.

AU - Iwakura, Yoichiro

AU - Gunnersen, Jennifer M.

AU - Stent, Andrew W.

AU - Godfrey, Dale I.

AU - Rossjohn, Jamie

AU - Westall, Glen P.

AU - Kjer-Nielsen, Lars

AU - Strugnell, Richard A.

AU - McCluskey, James

AU - Corbett, Alexandra J.

AU - Hinks, Timothy S.C.

AU - Chen, Zhenjun

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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 Legionellalongbeachae 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.

AB - 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 Legionellalongbeachae 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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Wang H, D’Souza C, Lim XY, Kostenko L, Pediongco TJ, Eckle SBG et al. MAIT cells protect against pulmonary Legionella longbeachae infection. Nature Communications. 2018 Dec 1;9(1). 3350. https://doi.org/10.1038/s41467-018-05202-8