Three Lines of Defense: Macrophage Subset Compartmentalization in Salmonella-Infected Peyer's Patches

Abstract

Background: Salmonella enterica serovar Typhimurium is a major enteric pathogen that invades the host via M cells overlying Peyer's patches. Macrophages are critical for host defense, yet the anatomical distribution of distinct macrophage subsets within Peyer's patches during active infection remains incompletely characterized.

Methods: Female C57BL/6 mice were orally infected with Salmonella Typhimurium strain SL1344 following streptomycin pretreatment. At 7 days post-infection, cecal Peyer's patches were examined macroscopically and by immunohistochemistry using antibodies against F4/80, Moma1, and Moma2.

Results: Infected mice exhibited marked cecal hyperemia, wall thickening, and enlarged Peyer's patches. F4/80⁺ macrophages densely accumulated in the subepithelial dome (SED) and were also observed in follicular periphery and perivascular areas. Moma1⁺ cells were sharply delineated around B-cell follicles and vessels, with no staining in SED or interfollicular regions (IFR). Moma2⁺ macrophages were widely distributed outside follicles, with highest density in IFR and around high endothelial venules.

Conclusion: Oral Salmonella infection induces compartmentalized redistribution of macrophage subsets in Peyer's patches. F4/80⁺ cells serve as first-line phagocytes at the bacterial entry site, Moma1⁺ cells function as barrier sentinels, and Moma2⁺ cells localize to T-cell zones for antigen presentation. This functional topography informs mucosal vaccine design.