Barrier immune memory is programmed by intestinal epithelial cell presentation of cytosol-delivered bacterial antigens.

Intestinal epithelial cells presenting cytosol-delivered bacterial antigens program robust barrier immune memory, with significantly enhanced responses compared to bacterial retention.

• Why it matters: Understanding how antigen localization influences immune responses is crucial for developing targeted mucosal vaccines and therapies, as current knowledge about antigen compartmentalization's role remains limited.
• What they did: Researchers tracked CD4 T cell responses to a single epitope in Citrobacter rodentium, comparing antigens retained within bacteria to those injected into colonocyte cytosol via a type III secretion system, and performed single-cell transcriptomics.
• The result: Cytosol-delivered antigens elicited strong mucosal CD4 T cell responses and epithelial-resident memory formation, driven by direct epithelial presentation and epithelial-T cell communication, highlighting nonprofessional antigen-presenting cells as key in shaping immune memory.