Macrophage MR1 antigen presentation promotes MAIT cell immunity and lung microbiota modulation
Mucosal-associated invariant T cells (MAIT cells) mediate tissue homeostasis and antimicrobial immunity. However, the cells that express major histocompatibility complex (MHC) class I-related protein 1 (MR1) and present microbial vitamin B-derived antigens (VitBAg) to MAIT cells remain unknown. We found that MR1 expression varied across tissues and cell types. Macrophages from the lung and peritoneal cavity expressed the highest levels of MR1 and were the most efficient at capturing and presenting VitBAg to MAIT cells. Expression of MR1 in macrophages was regulated transcriptionally and induced by the tissue environment and microbiota. Depletion of MR1 in macrophages, dendritic cells, and monocytes changed the composition of the microbiota and impaired MAIT cell responses against bacterial infection. We concluded that macrophages are key for MR1 antigen presentation and MAIT cell immunity.
Authors
- Tri Giang Phan (ORCID: https://orcid.org/0000-0002-4909-2984)
- X. Zhang (ORCID: https://orcid.org/0000-0002-7032-6722)
- Atieh Mousavizadeh (ORCID: https://orcid.org/0009-0008-8513-5022)
- Alexandra Jane Corbett (ORCID: https://orcid.org/0000-0003-1618-4337)
- Sinha Debajyoti (ORCID: https://orcid.org/0000-0002-4791-9036)
- Scott N. Mueller (ORCID: https://orcid.org/0000-0002-3838-3989)
- Yuting Yan (ORCID: https://orcid.org/0000-0001-7081-2037)
- Jóse A. Villadangos (ORCID: https://orcid.org/0000-0001-6771-8891)
- Hui‐Fern Koay (ORCID: https://orcid.org/0000-0002-3236-9609)
- Laura K. Mackay (ORCID: https://orcid.org/0000-0002-8496-6632)
- Jeffrey Y. W. Mak (ORCID: https://orcid.org/0000-0002-8011-4539)
- Antoine Roquilly (ORCID: https://orcid.org/0000-0002-1029-6242)
- Vanta Jameson
- David P. Fairlie (ORCID: https://orcid.org/0000-0002-7856-8566)
- Alexis Perez‐Gonzalez (ORCID: https://orcid.org/0000-0002-8674-2034)
- Ajithkumar Vasanthakumar (ORCID: https://orcid.org/0000-0002-1620-7781)
- Mitra Ashayeripanah (ORCID: https://orcid.org/0000-0001-8593-5996)
- T Poch (ORCID: https://orcid.org/0000-0001-8178-9522)
- Timothy P. Stinear (ORCID: https://orcid.org/0000-0003-0150-123X)
- Zhenjun Chen (ORCID: https://orcid.org/0000-0003-1205-683X)
- Laura E. Cook (ORCID: https://orcid.org/0000-0003-3153-2045)
- Hamish E. G. McWilliam (ORCID: https://orcid.org/0000-0003-3479-3419)
- Calum J. Walsh (ORCID: https://orcid.org/0000-0003-3113-9534)
- Emmanuel Montassier (ORCID: https://orcid.org/0000-0002-2313-1172)
- Yannick O. Alexandre (ORCID: https://orcid.org/0000-0002-6634-4098)
- Nikita Potemkin (ORCID: https://orcid.org/0000-0002-1459-751X)
- Jan Schroeder (ORCID: https://orcid.org/0000-0001-5270-0605)
- Abderrahman Hachani (ORCID: https://orcid.org/0000-0001-8032-2154)
- Jieru Deng (ORCID: https://orcid.org/0000-0002-7786-4961)
- Huimeng Wang (ORCID: https://orcid.org/0000-0003-0226-3982)
- Lachlan Dryburgh (ORCID: https://orcid.org/0009-0007-5579-7466)
- Jenny Kingham
Institutions
- Garvan Institute of Medical Research (AU)
- University of British Columbia (CA)
- Inserm (FR)
- The University of Melbourne (AU)
- La Trobe University (AU)
- Sichuan University (CN)
- Peter Doherty Institute (AU)
- St Vincent's Clinic (AU)
- Centre d'Investigation Clinique de Nantes (FR)
- ARC Centre of Excellence for Innovations in Peptide and Protein Science (AU)
- Olivia Newton-John Cancer Wellness & Research Centre (AU)
- Center for Research in Transplantation and Translational Immunology
- Nantes Université (FR)
- Tsinghua University (CN)
Publication Details
- Journal
- Science
- Published
- 2025-12-04
- DOI
- https://doi.org/10.1126/science.adr6322
- Citations
- 4
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 3.19