Intestinal villous M cells: An antigen entry site in the mucosal epithelium

Abstract

T he huge intestinal surface area is physically protected by a layer of tightly joined epithelial cells, which prevent most enteric environmental antigens from penetrating the host (1). However, entry into the host is made possible by a special gateway, comprised of M cells, located over organized mucosal lymphoid follicles such as Peyer's patches (PP). The M cells, characterized by an irregular brush border and reduced glycocalyx, efficiently take up and transport a wide variety of macromolecules and microorganisms from the gut lumen to the inside of the PP (2-6), which contain all of the necessary lymphoid cells for the induction and regulation of antigen-specific IgA responses (7). However, the origin of M cells and the regulation of their development are not understood. A previous study (8) The common mucosal immune system (CMIS), which connects the inductive (e.g., PP) and effector (e.g., lamina propria; LP) sites, has been shown to be a central pathway for the induction of antigen-specific IgA immune responses in the gastrointestinal tract (7). For example, oral administration of Salmonella typhimurium leads to the transport of the bacterial antigen from the lumen of the intestinal tract into the PP by means of M cells for the initial priming of antigen-specific CD4 ϩ T cells and IgA-committed B cells (12). These antigen-sensitized cells leave the PP and contribute to the subsequent induction of Salmonella-specific IgA response in the distant intestinal LP by means of CMIS. In addition to the wellcharacterized CMIS-dependent IgA induction pathway, recent evidence suggests the presence of an additional IgA induction pathway that is independently operated from the PP-originated CMIS (13-15). Interestingly, it also has been reported that induction of intestinal mucosal IgA against the commensal bacteria was independent from T cell help and organized lymphoid tissue (16). Further, our recent study (17) has demonstrated that antigenspecific IgA antibody responses can be induced in the absence of PP. These studies imply the existence of a PP-independent mucosal immune pathway for dietary antigen and bacteria uptake.A recent study (18) has suggested that the invasion gene (SPI1)-deficient S. typhimurium can be disseminated from the intestinal epithelium to the systemic compartment in the absence of PPassociated M cells by means of the CD18-dependent pathway. Further, dendritic cells in the lamina propria of the small intestine expressing tight junction protein offer another possible antigen uptake site (19). Thus, intestinal DCs are capable of extending dendrites to the lumen side by opening the tight junction. However, the exact mechanism for inducing Ag-specific immune responses independently of PP requires further elucidation.In this study, we have discovered intestinal villous M cells, which serve as an antigen gateway for the sampling of gut bacteria and subsequent induction of Ag-specific immune responses in a PPindependent manner. These lines of study are crucial for understanding the mechanisms of antige...

Indigenous opportunistic bacteria inhabit mammalian gut-associated lymphoid tissues and share a mucosal antibody-mediated symbiosis

“…S1A). Thus, although some antigen-sampling cells [e.g., villous M cells (15) and epithelial DCs (16)] are located in the epithelium covering the more diffuse LP region, it seems that antigen-sampling M cells and DCs in the follicle-associated epithelium of PPs are responsible for the entry of Alcaligenes. Furthermore, the presence of Alcaligenes inside PPs was demonstrated to be a common feature by the characterization of different species of mice housed in various SPF-maintained experimental animal facilities (Fig.…”

Persorption Mechanisms of Luminal Antigenic Particulates via Apoptotic Epithelial Cells of Intestinal Villi into Systemic Blood Circulation in Orally Immunized Rats

“…Special antigen-trapping cells, intestinal villous M cells, have been found in the intestinal villi of mice [20]. Villous M cells accompanied by intraepithelial pockets were detected in the villous epithelium by lectin histochemistry by means of UEA-1, and take up some species of bacteria [20].…”

“…Villous M cells accompanied by intraepithelial pockets were detected in the villous epithelium by lectin histochemistry by means of UEA-1, and take up some species of bacteria [20]. In our previous study of orally immunized rats, however, the antigenic molecule and its SpAb are absorbed by apoptotic microvillous columnar epithelial cells whose nuclear DNA is fragmented and which have no intraepithelial pockets [47].…”

Roundtrip Ticket for Secretory IgA: Role in Mucosal Homeostasis?

“…The differentiation and uptake processes of M cells are poorly defined (18), mainly because their scarcity in the intestinal mucosa has hampered their cellular and biochemical studies. The existence of M cells outside the FAE capable to sample Salmonella, Yersinia, and gut bacterial Ags has been reported in intestinal villi in mice devoid of Peyer's patches (19). Labeling with the novel M cell-specific marker secretory granule neuroendocrine protein-1 should help to establish the possibly related phenotype of such cells (20).…”