Abstract
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.
Highlights
In mammals, the gastrointestinal mucosa is the largest surface of interaction with the external environment
Peyer’s patches (PPs) plasmacytoid DCs (pDCs) are distinct from pDCs isolated from other tissues by their inability to secrete abundant type I IFN in response to the TLR9 agonist CpG (Table 2) [44]
We found that pDCs are mainly located in the interfollicular regions (IFR) but not in the subepithelial dome (SED) where BST2 is weakly displayed by monocyte-derived cells (Figure 4B)
Summary
The gastrointestinal mucosa is the largest surface of interaction with the external environment. The intestinal epithelium forms a physical barrier between the lumen and the lamina propria 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 [1]. 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 [13, 14] The latter display specific carbohydrates and receptors that are used as binding sites by pathogens [15,16,17,18,19,20,21,22]. We discuss alterations affecting the different phagocyte subsets upon PP stimulation or infection
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