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Sci Immunol. 2019 Nov 15;4(41). pii: eaaw0402. doi: 10.1126/sciimmunol.aaw0402.

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

Author information

1
Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
2
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China.
3
School of Medicine, Tsinghua University, Beijing, China.
4
Sir Peter MacCallum Department of Oncology, University of Melbourne, VIC 3010, Australia.
5
Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, University of Queensland, Saint Lucia, QLD 4072, Australia.
6
Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Queensland, Saint Lucia, QLD 4072, Australia.
7
QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia.
8
Infection and Immunity Program and the Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
9
Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, VIC 3800, Australia.
10
Institute of Infection and Immunity, Cardiff University, School of Medicine, Heath Park, CF14 4XN Wales, UK.
11
John Curtin School of Medical Research, The Australian National University, Acton, ACT 2601 Australia.
12
Discipline of Pathology, Charles Perkins Centre, Faculty of Medicine and Health, University of Sydney, Sydney, NSW 2006, Australia.
13
Biomedical Manufacturing, CSIRO, Parkville, VIC, 3052, Australia.
14
Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia. zhenjun@unimelb.edu.au corbetta@unimelb.edu.au rastru@unimelb.edu.au.

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.

PMID:
31732518
DOI:
10.1126/sciimmunol.aaw0402

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