MAIT cell plasticity enables functional adaptation that drives antibacterial immune protection
Mucosal-associated invariant T (MAIT) cells are known for their rapid effector functions and antibacterial immune protection. Here, we define the plasticity of interferon-γ (IFN-γ)-producing MAIT1 and interleukin-17A (IL-17A)-producing MAIT17 cell subsets in vivo. Whereas T-bet<sup>+</sup> MAIT1 cells remained stable in all experimental settings, after adoptive transfer or acute <i>Legionella</i> or <i>Francisella</i> infection, RORγt<sup>+</sup> MAIT17 cells could undergo phenotypic and functional conversion into both RORγt<sup>+</sup>T-bet<sup>+</sup> MAIT1/17 and RORγt<sup>-</sup>T-bet<sup>+</sup> MAIT1 cells. This plasticity ensured that MAIT17 cells played a dominant role in generating antibacterial MAIT1 responses in mucosal tissues. Single-cell transcriptomics revealed that MAIT17-derived MAIT1 cells were distinct from canonical MAIT1 cells yet could migrate out of mucosal tissues to contribute to the global MAIT1 pool in subsequent systemic infections. Human IL-17A-secreting MAIT cells also showed similar functional plasticity. Our findings have broad implications for understanding the role of MAIT cells in combatting infections and their potential utility in MAIT cell-targeted vaccines.
Authors
- Alexandra Jane Corbett (ORCID: https://orcid.org/0000-0003-1618-4337)
- Zhongfang Wang (ORCID: https://orcid.org/0000-0003-3236-5170)
- Adam G. Nelson (ORCID: https://orcid.org/0000-0002-5897-791X)
- Hyun Jae Lee (ORCID: https://orcid.org/0000-0002-9204-6078)
- Sidonia B. G. Eckle (ORCID: https://orcid.org/0000-0003-0766-171X)
- James McCluskey (ORCID: https://orcid.org/0000-0002-8597-815X)
- Bronwyn S. Meehan (ORCID: https://orcid.org/0000-0001-7368-2979)
- Jinhan Yu (ORCID: https://orcid.org/0000-0003-3807-2088)
- Jeffrey Y. W. Mak (ORCID: https://orcid.org/0000-0002-8011-4539)
- Ashraful Haque (ORCID: https://orcid.org/0000-0003-2260-0026)
- David P. Fairlie (ORCID: https://orcid.org/0000-0002-7856-8566)
- Zhenjun Chen (ORCID: https://orcid.org/0000-0003-1205-683X)
- Marcela L. Moreira (ORCID: https://orcid.org/0000-0003-3477-0727)
- Michael N. T. Souter (ORCID: https://orcid.org/0000-0002-1459-7923)
- Lucy J. Meehan (ORCID: https://orcid.org/0000-0001-8638-644X)
- Jan Schroeder (ORCID: https://orcid.org/0000-0001-5270-0605)
- Huimeng Wang (ORCID: https://orcid.org/0000-0003-0226-3982)
- Shihan Li (ORCID: https://orcid.org/0000-0003-3207-7064)
- Yuchen Zhou (ORCID: https://orcid.org/0000-0002-8239-8619)
Institutions
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Peking Union Medical College Hospital (CN)
- Peter Doherty Institute (AU)
- ARC Centre of Excellence for Innovations in Peptide and Protein Science (AU)
- State Key Laboratory of Respiratory Disease (CN)
- Guangzhou Medical University (CN)
- Tsinghua University (CN)
Publication Details
- Journal
- Science Immunology
- Published
- 2024-12-06
- DOI
- https://doi.org/10.1126/sciimmunol.adp9841
- Citations
- 20
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 4.81