MAIT cell plasticity enables functional adaptation that drives antibacterial immune protection.

Autor: Wang H; State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, Guangzhou Medical University, Guangzhou, China.; Department of Immunology and Microbiology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Souter MNT; Department of Immunology and Microbiology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., de Lima Moreira M; Department of Immunology and Microbiology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Li S; Department of Immunology and Microbiology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.; Computational Sciences Initiative, Department of Immunology and Microbiology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Zhou Y; Department of Immunology and Microbiology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.; Tsinghua Medicine, School of Medicine, Tsinghua University, Beijing, China., Nelson AG; Department of Immunology and Microbiology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Yu J; Department of Immunology and Microbiology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.; Department of Clinical Laboratory, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China., Meehan LJ; Department of Immunology and Microbiology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Meehan BS; Department of Immunology and Microbiology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Eckle SBG; Department of Immunology and Microbiology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Lee HJ; Department of Immunology and Microbiology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Schröder J; Department of Immunology and Microbiology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.; Computational Sciences Initiative, Department of Immunology and Microbiology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Haque A; Department of Immunology and Microbiology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Mak JYW; Centre for Chemistry and Drug Discovery and ARC Centre of Excellence for Innovations in Peptide and Protein Science, Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia., Fairlie DP; Centre for Chemistry and Drug Discovery and ARC Centre of Excellence for Innovations in Peptide and Protein Science, Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia., McCluskey J; Department of Immunology and Microbiology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Wang Z; State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, Guangzhou Medical University, Guangzhou, China., Chen Z; Department of Immunology and Microbiology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Corbett AJ; Department of Immunology and Microbiology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
Jazyk: angličtina
Zdroj: Science immunology [Sci Immunol] 2024 Dec 06; Vol. 9 (102), pp. eadp9841. Date of Electronic Publication: 2024 Dec 06.
DOI: 10.1126/sciimmunol.adp9841
Abstrakt: 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 + MAIT1 cells remained stable in all experimental settings, after adoptive transfer or acute Legionella or Francisella infection, RORγt + MAIT17 cells could undergo phenotypic and functional conversion into both RORγt + T-bet + MAIT1/17 and RORγt - T-bet + 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.
Databáze: MEDLINE