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Pathologic and physiologic interactions of bacteria with the gastrointestinal epithelium^1,2,3

¹ From Harvard Medical School, Boston, and the Mucosal Immunology Laboratory, Massachusetts General Hospital, Boston.

Communication between microorganisms and the gastrointestinal epithelium, ie, bacterial-epithelial "crosstalk," is examined. Because most basic research on the molecular inter-action of bacteria with the gut epithelium relates to pathogen-enterocyte 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 the mucosal barrier. Salmonella enterica typhimurium interacts with the physiologic receptor for epidermal growth factor to co-opt the receptor's signal transduc-tion mechanisms. Enteropathic Escherichia coli secretes a recep-tor (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 is used to illustrate how pathogens use the follicular epithelial cell (M cell), the phys-iologic conduit for antigens to reach gut associated-lymphoid tis-sues, 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 vac-uole and co-opts actin and myosin to form a propelling tail for further penetration of the epithelium through the basolateral sur-face. 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.

Key Words: Epithelial-microbial crosstalk • type III secretion • probiotics • intestinal epithelium • Salmonella enterica typhimurium • Escherichia coli • Shigella flexneri

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