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The gut represents a potential entry site for a wide range of pathogens including protozoa, bacteria, viruses, or fungi. Consequently, it is protected by one of the largest and most diversified population of immune cells of the body. Its surveillance requires the constant sampling of its encounters by dedicated sentinels composed of follicles and their associated epithelium located in specialized area. In the small intestine, Peyer’s patches (PPs) are the most important of these mucosal immune response inductive sites. Through several mechanisms including transcytosis by specialized epithelial cells called M-cells, access to the gut lumen is facilitated in PPs. Although antigen sampling is critical to the initiation of the mucosal immune response, pathogens have evolved strategies to take advantage of this permissive gateway to enter the host and disseminate. It is, therefore, critical to decipher the mechanisms that underlie both host defense and pathogen subversive strategies in order to develop new mucosal-based therapeutic approaches.

Whereas penetration of pathogens through M cells has been well described, their fate once they have reached the subepithelial dome (SED) remains less well understood. Nevertheless, it is clear that the mononuclear phagocyte system (MPS) plays a critical role in handling these pathogens. MPS members, including both dendritic cells and macrophages, are indeed strongly enriched in the SED, interact with M cells, and are necessary for antigen presentation to immune effector cells. This review focuses on recent advances, which have allowed distinguishing the different PP mononuclear phagocyte subsets. It gives an overview of their diversity, specificity, location, and functions. Interaction of PP phagocytes with the microbiota and the follicle-associated epithelium as well as PP infection studies are described in the light of these new criteria of PP phagocyte identification. Finally, known alterations affecting the different phagocyte subsets during PP stimulation or infection are discussed.

Introduction In mammals, the gastrointestinal mucosa is the largest surface of interaction with the external environment. Warhammer 40k 3d files stl post. This ensures an efficient absorption of nutrients, electrolytes, and water but concomitantly it exposes the body to environmental threats through the ingestion of contaminated food or drinks.

Thus, the gut represents a privileged site of entry for various pathogen agents, such as protozoa, bacteria, viruses, toxins, or prion. Different mechanisms of defense exist to protect the body integrity against these threats. The efficient and size-selective shield provided by the mucus layer and the glycocalyx above the villous epithelium favors the uptake of small diffusible molecules while preventing microorganisms from reaching the epithelium.

Protection is also ensured through secretion of antimicrobial compounds and innate polyreactive and antigen-specific secretory immunoglobulin A (sIgA) in the intestinal lumen. Finally, the intestinal epithelium forms a physical barrier between the lumen and the lamina propria. However, pathogens, such as Salmonella and Shigella, can survive challenging environmental conditions, disrupt the mucus and the continuity of the epithelial barrier, and penetrate the epithelium to reach interstitial tissues (). It is, therefore, important for the mucosal immune system to be aware of the presence of pathogens as soon as possible. A simple way to achieve this objective is to provide a facilitated access to the gut luminal content toward the mucosal surface at restricted areas distributed regularly along the gastrointestinal tract. 1001 vinhos para beber antes de morrer pdf gratis. The mammal small intestine possesses such specific sentinel sites marked by the presence of lymphoid follicles.

Peyer’s patches (PPs) are the most important of these monitoring sites since they are constituted of several clustered B-cell follicles forming domes interspersed with T-cell zones termed interfollicular regions (IFR). While villi are specialized for absorption of nutrients, PPs are dedicated to the sampling of foreign material and to the induction of mucosal immune responses (–). Due to the low number of mucus-secreting goblet cells and lack of polymeric immunoglobulin receptor expression in the follicle-associated epithelium (FAE), PP have a reduced mucus layer and no IgA secretion, respectively, which may favor interaction with pathogens (, ). Moreover, the FAE is characterized by the presence of specialized epithelial cells termed M cells, which lack a typical brush border and possess a thin glycocalyx that give a better accessibility to large particulate antigens (–). The underlying stromal cell network ensures at least in part this specialization of the FAE. Thus, subepithelial stromal cells express high amounts of the cytokine RANKL, which is necessary to both the production of the chemokine CCL20 by the FAE and the development of M cells (, ). The latter display specific carbohydrates and receptors that are used as binding sites by pathogens (–).