Membranous (M) cells are specialized epithelial antigentransporting cells scattered in the follicle-associated epithelium covering the gut lymphoid follicles such as Peyer's patches. Although the importance of M cells as a main portal for luminal antigens has long been recognized, molecular mechanisms for M-cell antigen uptake has remained largely elusive. We have recently found that glycoprotein 2 (GP2) is exclusively expressed on M cells among intestinal epithelial cells and serves as an uptake receptor for a subset of commensal and pathogenic bacteria. GP2 interacts with FimH, a major component of the type 1 pilus on the outer membrane of a subset of gram-negative enterobacilli such as E. coli and Salmonella enterica. Furthermore, GP2-FimH interaction is necessary for efficient uptake of FimH+ bacteria by M cells and subsequent bacteria- specific mucosal immune responses. Pancreatic GP2 may also be involved in innate immunity by 'opsonization' of FimH+ bacteria to facilitate their egestion in feces as well as translocation across the intestinal epithelium.
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