IL-23 costimulates antigen-specific MAIT cell activation and enables vaccination against bacterial infection

Huimeng Wang; Lars Kjer-Nielsen; Mai Shi; Criselle D'Souza; Troi J. Pediongco; Hanwei Cao; Lyudmila Kostenko; Xin Yi Lim; Sidonia B.G. Eckle; Bronwyn S. Meehan; Tianyuan Zhu; Bingjie Wang; Zhe Zhao; Jeffrey Y.W. Mak; David P. Fairlie; Michele W.L. Teng; Jamie Rossjohn; Di Yu; Barbara Fazekas De St Groth; George Lovrecz; Louis Lu; James McCluskey; Richard A. Strugnell; Alexandra J. Corbett; Zhenjun Chen

doi:10.1126/sciimmunol.aaw0402

IL-23 costimulates antigen-specific MAIT cell activation and enables vaccination against bacterial infection

Huimeng Wang, Lars Kjer-Nielsen, Mai Shi, Criselle D'Souza, Troi J. Pediongco, Hanwei Cao, Lyudmila Kostenko, Xin Yi Lim, Sidonia B.G. Eckle, Bronwyn S. Meehan, Tianyuan Zhu, Bingjie Wang, Zhe Zhao, Jeffrey Y.W. Mak, David P. Fairlie, Michele W.L. Teng, Jamie Rossjohn, Di Yu, Barbara Fazekas De St Groth, George LovreczLouis Lu, James McCluskey, Richard A. Strugnell, Alexandra J. Corbett, Zhenjun Chen^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

70 Citations (Scopus)

Abstract

Mucosal-associated invariant T (MAIT) cells are activated in a TCR-dependent manner by antigens derived from the riboflavin synthesis pathway, including 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil (5-OP-RU), bound to MHC-related protein-1 (MR1). However, MAIT cell activation in vivo has not been studied in detail. Here, we have found and characterized additional molecular signals required for optimal activation and expansion of MAIT cells after pulmonary Legionella or Salmonella infection in mice. We show that either bone marrow-derived APCs or non-bone marrow-derived cells can activate MAIT cells in vivo, depending on the pathogen. Optimal MAIT cell activation in vivo requires signaling through the inducible T cell costimulator (ICOS), which is highly expressed on MAIT cells. Subsequent expansion and maintenance of MAIT-17/1-type responses are dependent on IL-23. Vaccination with IL-23 plus 5-OP-RU augments MAIT cell-mediated control of pulmonary Legionella infection. These findings reveal cellular and molecular targets for manipulating MAIT cell function under physiological conditions.

Original language	English
Article number	eaaw0402
Journal	Science immunology
Volume	4
Issue number	41
DOIs	https://doi.org/10.1126/sciimmunol.aaw0402
Publication status	Published - 15 Nov 2019

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Wang, H., Kjer-Nielsen, L., Shi, M., D'Souza, C., Pediongco, T. J., Cao, H., Kostenko, L., Lim, X. Y., Eckle, S. B. G., Meehan, B. S., Zhu, T., Wang, B., Zhao, Z., Mak, J. Y. W., Fairlie, D. P., Teng, M. W. L., Rossjohn, J., Yu, D., De St Groth, B. F., ... Chen, Z. (2019). IL-23 costimulates antigen-specific MAIT cell activation and enables vaccination against bacterial infection. Science immunology, 4(41), Article eaaw0402. https://doi.org/10.1126/sciimmunol.aaw0402

@article{afe5b3b82c9144808d3d46e383d2a979,

title = "IL-23 costimulates antigen-specific MAIT cell activation and enables vaccination against bacterial infection",

abstract = "Mucosal-associated invariant T (MAIT) cells are activated in a TCR-dependent manner by antigens derived from the riboflavin synthesis pathway, including 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil (5-OP-RU), bound to MHC-related protein-1 (MR1). However, MAIT cell activation in vivo has not been studied in detail. Here, we have found and characterized additional molecular signals required for optimal activation and expansion of MAIT cells after pulmonary Legionella or Salmonella infection in mice. We show that either bone marrow-derived APCs or non-bone marrow-derived cells can activate MAIT cells in vivo, depending on the pathogen. Optimal MAIT cell activation in vivo requires signaling through the inducible T cell costimulator (ICOS), which is highly expressed on MAIT cells. Subsequent expansion and maintenance of MAIT-17/1-type responses are dependent on IL-23. Vaccination with IL-23 plus 5-OP-RU augments MAIT cell-mediated control of pulmonary Legionella infection. These findings reveal cellular and molecular targets for manipulating MAIT cell function under physiological conditions.",

author = "Huimeng Wang and Lars Kjer-Nielsen and Mai Shi and Criselle D'Souza and Pediongco, {Troi J.} and Hanwei Cao and Lyudmila Kostenko and Lim, {Xin Yi} and Eckle, {Sidonia B.G.} and Meehan, {Bronwyn S.} and Tianyuan Zhu and Bingjie Wang and Zhe Zhao and Mak, {Jeffrey Y.W.} and Fairlie, {David P.} and Teng, {Michele W.L.} and Jamie Rossjohn and Di Yu and {De St Groth}, {Barbara Fazekas} and George Lovrecz and Louis Lu and James McCluskey and Strugnell, {Richard A.} and Corbett, {Alexandra J.} and Zhenjun Chen",

note = "Publisher Copyright: {\textcopyright} 2019 The Authors.",

year = "2019",

month = nov,

day = "15",

doi = "10.1126/sciimmunol.aaw0402",

language = "English",

volume = "4",

journal = "Science immunology",

issn = "2470-9468",

publisher = "American Association for the Advancement of Science",

number = "41",

}

Wang, H, Kjer-Nielsen, L, Shi, M, D'Souza, C, Pediongco, TJ, Cao, H, Kostenko, L, Lim, XY, Eckle, SBG, Meehan, BS, Zhu, T, Wang, B, Zhao, Z, Mak, JYW, Fairlie, DP, Teng, MWL, Rossjohn, J, Yu, D, De St Groth, BF, Lovrecz, G, Lu, L, McCluskey, J, Strugnell, RA, Corbett, AJ & Chen, Z 2019, 'IL-23 costimulates antigen-specific MAIT cell activation and enables vaccination against bacterial infection', Science immunology, vol. 4, no. 41, eaaw0402. https://doi.org/10.1126/sciimmunol.aaw0402

TY - JOUR

T1 - IL-23 costimulates antigen-specific MAIT cell activation and enables vaccination against bacterial infection

AU - Wang, Huimeng

AU - Kjer-Nielsen, Lars

AU - Shi, Mai

AU - D'Souza, Criselle

AU - Pediongco, Troi J.

AU - Cao, Hanwei

AU - Kostenko, Lyudmila

AU - Lim, Xin Yi

AU - Eckle, Sidonia B.G.

AU - Meehan, Bronwyn S.

AU - Zhu, Tianyuan

AU - Wang, Bingjie

AU - Zhao, Zhe

AU - Mak, Jeffrey Y.W.

AU - Fairlie, David P.

AU - Teng, Michele W.L.

AU - Rossjohn, Jamie

AU - Yu, Di

AU - De St Groth, Barbara Fazekas

AU - Lovrecz, George

AU - Lu, Louis

AU - McCluskey, James

AU - Strugnell, Richard A.

AU - Corbett, Alexandra J.

AU - Chen, Zhenjun

PY - 2019/11/15

Y1 - 2019/11/15

N2 - Mucosal-associated invariant T (MAIT) cells are activated in a TCR-dependent manner by antigens derived from the riboflavin synthesis pathway, including 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil (5-OP-RU), bound to MHC-related protein-1 (MR1). However, MAIT cell activation in vivo has not been studied in detail. Here, we have found and characterized additional molecular signals required for optimal activation and expansion of MAIT cells after pulmonary Legionella or Salmonella infection in mice. We show that either bone marrow-derived APCs or non-bone marrow-derived cells can activate MAIT cells in vivo, depending on the pathogen. Optimal MAIT cell activation in vivo requires signaling through the inducible T cell costimulator (ICOS), which is highly expressed on MAIT cells. Subsequent expansion and maintenance of MAIT-17/1-type responses are dependent on IL-23. Vaccination with IL-23 plus 5-OP-RU augments MAIT cell-mediated control of pulmonary Legionella infection. These findings reveal cellular and molecular targets for manipulating MAIT cell function under physiological conditions.

AB - Mucosal-associated invariant T (MAIT) cells are activated in a TCR-dependent manner by antigens derived from the riboflavin synthesis pathway, including 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil (5-OP-RU), bound to MHC-related protein-1 (MR1). However, MAIT cell activation in vivo has not been studied in detail. Here, we have found and characterized additional molecular signals required for optimal activation and expansion of MAIT cells after pulmonary Legionella or Salmonella infection in mice. We show that either bone marrow-derived APCs or non-bone marrow-derived cells can activate MAIT cells in vivo, depending on the pathogen. Optimal MAIT cell activation in vivo requires signaling through the inducible T cell costimulator (ICOS), which is highly expressed on MAIT cells. Subsequent expansion and maintenance of MAIT-17/1-type responses are dependent on IL-23. Vaccination with IL-23 plus 5-OP-RU augments MAIT cell-mediated control of pulmonary Legionella infection. These findings reveal cellular and molecular targets for manipulating MAIT cell function under physiological conditions.

UR - http://www.scopus.com/inward/record.url?scp=85075114723&partnerID=8YFLogxK

U2 - 10.1126/sciimmunol.aaw0402

DO - 10.1126/sciimmunol.aaw0402

M3 - Article

SN - 2470-9468

VL - 4

JO - Science immunology

JF - Science immunology

IS - 41

M1 - eaaw0402

ER -

IL-23 costimulates antigen-specific MAIT cell activation and enables vaccination against bacterial infection

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