A Unique Subset of Peyer's Patches Express Lysozyme

Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, Massachusetts.
Gastroenterology (Impact Factor: 16.72). 11/2009; 138(1):36-9. DOI: 10.1053/j.gastro.2009.11.033
Source: PubMed
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    ABSTRACT: The innate immune system plays a crucial role in maintaining the integrity of the intestine and protecting the host against a vast number of potential microbial pathogens from resident and transient gut microflora. Mucosal epithelial cells and Paneth cells produce a variety of antimicrobial peptides (defensins, cathelicidins, crytdinrelated sequence peptides, bactericidal/permeabilityincreasing protein, chemokine CCL20) and bacteriolytic enzymes (lysozyme, group IIA phospholipase A2) that protect mucosal surfaces and crypts containing intestinal stem cells against invading microbes. Many of the intestinal antimicrobial molecules have additional roles of attracting leukocytes, alarming the adaptive immune system or neutralizing proinflammatory bacterial molecules. Dysfunction of components of the innate immune system has recently been implicated in chronic inflammatory bowel diseases such as Crohn's disease and ulcerative colitis, illustrating the pivotal role of innate immunity in maintaining the delicate balance between immune tolerance and immune response in the gut.
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    ABSTRACT: We have recently demonstrated the presence of three populations of dendritic cells (DC) in the murine Peyer's patch. CD11b(+)/CD8alpha(-) (myeloid) DCs are localized in the subepithelial dome, CD11b(-)/CD8alpha(+) (lymphoid) DCs in the interfollicular regions, and CD11b(-)/CD8alpha(-) (double-negative; DN) DCs at both sites. We now describe the presence of a novel population of intraepithelial DN DCs within the follicle-associated epithelium and demonstrate a predominance of DN DCs only in mucosal lymphoid tissues. Furthermore, we demonstrate that all DC subpopulations maintain their surface phenotype upon maturation in vitro, and secrete a distinct pattern of cytokines upon exposure to T cell and microbial stimuli. Only myeloid DCs from the PP produce high levels of IL-10 upon stimulation with soluble CD40 ligand(-) trimer, or Staphylococcus aureus and IFN-gamma. In contrast, lymphoid and DN, but not myeloid DCs, produce IL-12p70 following microbial stimulation, whereas no DC subset produces IL-12p70 in response to CD40 ligand trimer. Finally, we show that myeloid DCs from the PP are particularly capable of priming naive T cells to secrete high levels of IL-4 and IL-10, when compared with those from nonmucosal sites, while lymphoid and DN DCs from all tissues prime for IFN-gamma production. These findings thus suggest that DC subsets within mucosal tissues have unique immune inductive capacities.
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    ABSTRACT: Paneth cells, highly secretory epithelial cells found at the bases of small intestinal crypts, release a variety of microbicidal molecules, including α-defensins and lysozyme. The secretion of antimicrobials by Paneth cells is thought to be important in mucosal host defense against invasion by enteric pathogens. We explored whether enteric pathogens can interfere with this arm of defense. We found that oral inoculation of mice with wild-type Salmonella enterica serovar Typhimurium decreases the expression of α-defensins (called cryptdins in mice) and lysozyme. Oral inoculation with Salmonella serovar Typhimurium strains that are heat killed, lack the PhoP regulon, and lack the SPI1 type III secretion system or with Listeria monocytogenes does not have this effect. Salmonella may gain a specific survival advantage in the intestinal lumen by decreasing the expression of microbicidal peptides in Paneth cells through direct interactions between Salmonella and the small intestinal epithelium.
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