Intestinal Defenses Maintenance of Intestinal Barrier Function in Host Defense

Intestinal Defenses Maintenance of Intestinal Barrier Function in Host Defense

Gareau Melanie G, Perdue Mary H, Sherman Philip M
US Gastroenterology Review 2007 - Issue II - October 2007
Published: October 2008
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The intestinal mucosa represents an important interface between host epithelial cells, microbes, and antigens. The epithelial cell lining forms a selective barrier that allows the transport of nutrients, while at the same time preventing uptake of noxious antigens and luminal bacteria. With an estimated surface area of more than 200m2, the intestinal epithelium must adequately protect itself from potential pathogens. Protective mechanisms including physical, chemical, and immunological barriers are in place to maintain homeostasis. A breach in any one of these barriers by microbial pathogens can lead to disease. Enterohemorrhagic Escherichia coli (EHEC O157:H7) is a food-borne, pathogenic bacterium associated with abdominal cramping, diarrhea, bloody diarrhea (referred to as hemorrhagic colitis), and kidney failure due to the hemolytic-uremic syndrome. Recent outbreaks from consumption of contaminated spinach and water sources are examples of the importance of barrier protection against pathogenic bacteria.1

Mucosal Barrier
Epithelial cells serve as the surface layer lining the gut and, as such, provide the first line of defense against threats from luminal antigens and microbes. It comprises a single layer of polarized, columnar epithelial cells supported by a fibroblast sheath. The underlying lamina propria contains a host of immune cells and nerve fibers, as well as endothelial cells comprising blood vessels. The rest of the gut wall is composed of the muscularis mucosa, the submucosal plexus, and the serosa.

Interspersed between epithelial cells along the crypt–villus axis are goblet, Paneth, and enteroendocrine cells, which are all vital in maintaining mucosal protection. Enterochromaffin (EC) cells are a subtype of enteroendocrine cells that produce serotonin in response to luminal stimulation. EC cells act as sensory transducers to luminal changes in acidity, osmolarity, and nutrients, including amino acids and free fatty acids,2 as well as pathogens and bacterially derived toxins. Serotonin is contained in basolaterally located granules and released both constitutively and following stimulation into the lamina propria, where it can activate nerve fibers2 and subsequently cause goblet-cell-derived mucin secretion and passive water flux to wash away noxious antigens. The congenital absence of EC cells in the intestine resulting from a mutation in the neurogenin-3 gene causes chronic malabsorptive diarrhea,3 highlighting the importance of these cells in maintaining fluid and ion transport.

Goblet cells are specialized epithelial cells that produce a viscous glycoprotein made up mainly of secreted and membrane-bound mucin glycoproteins.4 Mucus forms a protective layer above the surface epithelium to prevent adherence of luminal bacteria and provide lubrication for propulsion of gut contents. Along with mucins, the trefoil factor family (TFF) of peptides is secreted by goblet cells, and is also important in defense and repair following injury.5 Specifically, TFF3 increases transepithelial resistance by increasing the expression of intercellular tight junction proteins in polarized epithelial monolayers.6

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