Pathogenic bacteria and dead cells are internalized by a unique subset of Peyer's patch dendritic cells that express lysozyme.

BACKGROUND & AIMS: Lysozyme has an important role in preventing bacterial infection. In the gastrointestinal tract, lysozyme is thought to be mainly expressed by Paneth cells of the crypt epithelium. We investigated its expression in the Peyer's patch, a major intestinal site of antigen sampling and pathogen entry. METHODS: We performed immunostaining on normal and Salmonella Typhimurium-infected intestinal samples and analyzed them by confocal microscopy and flow cytometry. RESULTS: In Peyer's patch of mouse, rat, and human, lysozyme was strongly expressed in the germinal center of follicles by tingible body macrophages and in the subepithelial dome by a subset of myeloid dendritic cells (DC). Among DC subsets from mouse Peyer's patches, these lysozyme-expressing DC displayed the highest surface expression of class II major histocompatibility complex and costimulatory molecules; they were the most efficient at capturing microspheres in vitro. Moreover, they were the main DC subset involved in bacterial pathogen uptake and in dead cell clearance, including M cells. CONCLUSIONS: The subepithelial dome of Peyer's patches contains a unique population of intestinal DC that secretes high levels of lysozyme and internalizes bacteria and dead cells.

Differentiation Paths of Peyer's Patch LysoDCs Are Linked to Sampling Site Positioning, Migration, and T Cell Priming.

The monocyte-derived phagocytes termed LysoDCs are hallmarks of Peyer's patches, where their main function is to sample intestinal microorganisms. Here, we study their differentiation pathways in relation with their sampling, migratory, and T cell-priming abilities. Among four identified LysoDC differentiation stages displaying similar phagocytic activity, one is located in follicles, and the others reside in subepithelial domes (SED), where they proliferate and mature as they get closer to the epithelium. Mature LysoDCs but not macrophages express a gene set in common with conventional dendritic cells and prime naive helper T cells in vitro. At steady state, they do not migrate into naive T cell-enriched interfollicular regions (IFRs), but upon stimulation, they express the chemokine receptor CCR7 and migrate from SED to the IFR periphery, where they strongly interact with proliferative immune cells. Finally, we show that LysoDCs populate human Peyer's patches, strengthening their interest as targets for modulating intestinal immunity.