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

Intestinal epithelial cell presentation of cytosol-delivered bacterial antigens programs robust mucosal CD4 T cell responses and epithelial-resident memory in mice.

• Why it matters: Understanding how antigen localization influences immune responses is crucial for developing effective mucosal vaccines and therapies. The role of nonprofessional antigen-presenting cells in shaping T cell memory was previously unclear.
• What they did: The study tracked CD4 T cell responses to a single epitope from Citrobacter rodentium, comparing antigens retained within bacteria versus those injected into colonocyte cytosol via a type III secretion system, using clonal tracking and single-cell transcriptomics.
• The result: Cytosol-delivered antigens elicited strong mucosal CD4 T cell responses and promoted epithelial-resident memory formation, driven by direct epithelial cell presentation and bidirectional communication that favored tissue residency over central memory differentiation.