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

Area of Science:

• Immunology
• Microbiology
• Cell Biology

Background:

• Mucosal associated invariant T (MAIT) cells are vital for immune responses.
• The specific cells presenting antigens to MAIT cells via MHC class I-related protein 1 (MR1) were previously unidentified.

Purpose of the Study:

• To identify the cells responsible for MR1-mediated antigen presentation to MAIT cells.
• To investigate the regulation and function of MR1 expression in antigen presentation.

Main Methods:

• Analysis of MR1 expression across various tissues and cell types.
• Functional assays assessing antigen capture and presentation by macrophages.
• Investigating the transcriptional regulation of MR1.
• In vivo studies involving depletion of MR1-expressing cells.

Main Results:

• MR1 expression levels varied significantly between tissues and cell types.
• Macrophages, particularly in the lung and peritoneal cavity, showed high MR1 expression and efficient presentation of microbial vitamin B-derived antigens (VitBAg).
• MR1 expression in macrophages is transcriptionally regulated and influenced by the tissue microenvironment and microbiota.
• Depletion of MR1-expressing cells altered microbiota composition and compromised MAIT cell responses during bacterial infection.

Conclusions:

• Macrophages are identified as critical cells for MR1-based antigen presentation to MAIT cells.
• The findings highlight the role of macrophages in MAIT cell-mediated immunity and tissue homeostasis.
• MR1 expression on macrophages is dynamically regulated and essential for effective antimicrobial responses.