Pathologic and physiologic interactions of bacteria with the gastrointestinal epithelium1–3
Lei Lu and W Allan Walker
ABSTRACT Communication between microorganisms and the gastrointestinal epithelium, ie, bacterial-epithelial “crosstalk,” is examined. Because most basic research on the molecular interaction of bacteria with the gut epithelium relates to pathogenenterocyte interaction,crosstalk with pathologic bacterial is considered in detail. Through their interactions with the intestinal epithelium, pathogens can modify epithelium function to enhance their penetration across the epithelial barrier and to exploit mucosal host defenses for their own benefit. Three representative pathogens are used to illustrate the various adaptive techniques used to colonize and penetrate themucosal barrier. Salmonella enterica typhimurium interacts with the physiologic receptor for epidermal growth factor to co-opt the receptor’s signal transduction mechanisms. Enteropathic Escherichia coli secretes a receptor (type III secretion) into the microvillus surface of enterocytes that disrupts the microvillus and alters its actin structure to form a dome-like anchoring site. Shigella flexneri isused to illustrate how pathogens use the follicular epithelial cell (M cell), the physiologic conduit for antigens to reach gut associated-lymphoid tissues, for penetration of the epithelial barrier. Shigella organisms attached to M cells use their endocytotic properties to enter the cell. Once inside the cell, the organism lyses the endocytic vacuole and co-opts actin and myosin to form apropelling tail for further penetration of the epithelium through the basolateral surface. Probiotics can protect the intestine by competing with pathogens for attachment, strengthening tight junctions between enterocytes, and enhancing the mucosal immune response to pathogens. However, additional molecular studies are needed to define more precisely the mechanism of probiotic-epithelial crosstalk. Am JClin Nutr 2001;73(suppl):1124S–30S. KEY WORDS Epithelial-microbial crosstalk, type III secretion, probiotics, intestinal epithelium, Salmonella enterica typhimurium, Escherichia coli, Shigella flexneri
tions, the epithelium is armed with active means of keeping intestinal bacteria in check (2). The intestinal epithelium must also be able to readily discriminate between resident ﬂora andenteric pathogens. The interactions between both enteropathogenic bacteria and resident ﬂora with the intestine is the focus of this review. A particular emphasis will be the signaling pathways used in this “crosstalk” between enteric pathogens and their intestinal host. Bacterial pathogens possess highly specialized adaptive processes that enable them to co-opt epithelial cell functions to augmenttheir penetration of the host intestinal epithelium to cause disease. A necessary step in the successful colonization and ultimate production of disease is the ability of bacterial pathogens to adhere to host surfaces, which is an important determinant of virulence. Generally, binding to intestinal host cells is essential for the bacteria to resist the ﬂuid ﬂow of the luminal contents and theperistalsis of intestinal contraction. Once bound to the epithelial surface, bacteria may colonize and establish a permanent residence in the gut. Bacterial adhesion to host cells or surfaces is often an essential ﬁrst stage in the disease process because pathogens have become localized to an appropriate target site. A wide range of mammalian cell surface constituents, including glycoproteins andglycolipids, can serve as receptors for bacterial attachment (3). The host cell is often an active participant in the adhesion process and does not function simply as an inert surface for attachment. Many pathogens possess a speciﬁc set of virulence factors that have evolved to affect the host. On the other hand, the host in turn has specialized strategies to resist such infections, often in response to...
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