Macrophage MR1 antigen presentation promotes MAIT cell immunity and lung microbiota modulation

• 成果类型: Article
• 署名作者: Deng, Jieru; Yan, Yuting; Zhang, Xiaoyue; Walsh, Calum J.; Montassier, Emmanuel; Sinha, Debajyoti; Wang, Huimeng; Mousavizadeh, Atieh; Ashayeripanah, Mitra; Mak, Jeffrey Y. W.; Koay, Hui-Fern; Poch, Tobias; Alexandre, Yannick O.; Mueller, Scott N.; Vasanthakumar, Ajithkumar; Stinear, Tim P.; Jameson, Vanta J.; Perez-Gonzalez, Alexis; Kingham, Jenny; Phan, Tri Giang; Potemkin, Nikita; Dryburgh, Lachlan; Schroeder, Jan; Fairlie, David P.; Mackay, Laura K.; Chen, Zhenjun; Cook, Laura; Hachani, Abderrahman; Corbett, Alexandra J.; Roquilly, Antoine; Villadangos, Jose A.; McWilliam, Hamish E. G.
• 署名单位: University of Melbourne; Peter Doherty Institute; Tsinghua University; Sichuan University; University of Melbourne; Peter Doherty Institute; Nantes Universite; Institut National de la Sante et de la Recherche Medicale (Inserm); CHU de Nantes; Institut National de la Sante et de la Recherche Medicale (Inserm); Nantes Universite; CHU de Nantes; University of Queensland; University of Queensland; ARC Centre of Excellence for Innovations in Peptide & Protein Science; La Trobe University; Olivia Newton-John Cancer Research Institute; La Trobe University; University of Melbourne; Garvan Institute of Medical Research; University of New South Wales Sydney; University of Melbourne; Peter Doherty Institute; University of Melbourne; University of British Columbia; University of Melbourne
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.adr6322
• 发表日期: 2026-01-15
• 页码: eadr6322
• 关键词: invariant t-cells; gene; activation; molecules; signals

摘要

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.