Microfold (M) cells are a type of epithelial cell specialized for antigen uptake and are present within many mucosal associated lymphoid tissues (MALT). These M cells vary in different MALT tissues with regard to their surface receptors, apical morphology, and function. In the small intestine, M cells are found more abundantly in the distal portion than in the proximal portion. In the presence of cholera toxin (CT), a bacterial toxin secreted from Vibrio cholerae, M cell clusters are induced on villous tips 48 hours post-administration. This study has determined that CT-induced M cell clusters are phenotypically different from other intestinal M cells and allow for greater bacterial adherence. This is potentially due to their absence or the reorganization of microvilli, which in theory disperses and/or lowers the electrostatic repulsion towards luminal microparticles. We see similar microvilli effacement in in vitro Caco2 BBe cultures, where cells treated with CT produce bare apical surfaces. This is not an effect from glycoprotein linkage depletion, which would affect microvilli structure. It remains to be determined whether the M cell clustering and microvilli effacement are more beneficial to the host, for immunosurveillance, or invading pathogens that take advantage of the apical change for colonization. These phenotypic changes could be utilized for rationally targeting therapeutics for uptake by M cells.

Intestinal M (microfold) cells are specialized epithelial cells overlying lymphoid tissues in the small intestine. Unlike common enterocytes, M cells lack an organized apical brush border, and are able to transcytose microparticles across the mucosal barrier to underlying antigen-presenting cells. We found that in both the dextran sodium sulfate and Citrobacter rodentium models of colitis, significantly increased numbers of Peyer's patch (PP) phenotype M cells were induced at the peak of inflammation in colonic epithelium, often accompanied by loosely organized lamina propria infiltrates. PP type M cells are thought to be dependent on cytokines, including tumor necrosis factor (TNF)-α and receptor activator of nuclear factor kappa-B ligand; these cytokines were also found to be induced in the inflamed tissues. The induction of M cells was abrogated by anti-TNF-α blockade, suggesting that anti-TNF-α therapies may have similar effects in clinical settings, although the functional consequences are not clear. Our results suggest that inflammatory cytokine-induced PP type M cells may be a useful correlate of chronic intestinal inflammation.