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Departments of
*
Pediatrics,
Medicine, and
Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814;
Department of Pediatrics, Walter Reed Army Medical Center, Washington, D.C. 20307;
¶ Department of Medicine, University of Cincinnati, and Cincinnati Veterans Administration Center, Cincinnati, OH 45220; and
|| Nutrient Requirements and Function Laboratory, Beltsville Human Nutrition and Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705
Infection with gastrointestinal nematodes exerts profound effects on both the immune and physiological responses of the host. We showed previously that the Th2 cytokines, IL-4 and IL-13, induce STAT6-dependent changes in intestinal epithelial cell permeability, absorption, and secretion that are similar to those observed in a secondary infection with Heligmosomoides polygyrus. In the current study we investigated whether nematode-induced effects on epithelial cell function were 1) generic, 2) dependent upon STAT6, and 3) attributable to direct effects on the epithelial cells themselves or mediated by effects on enteric nerves. Our results demonstrate that infection of BALB/c mice with three different gastrointestinal nematodes (H. polygyrus, Nippostrongylus brasiliensis, and Trichinella spiralis) alters intestinal epithelial cell function by decreasing resistance, glucose absorption, and secretory responses to 5-hydroxytryptamine and acetylcholine, two critical mediators in the submucosal reflex pathway. These modified responses are dependent on STAT6 and are the result of both direct effects and indirect effects mediated through enteric nerves.
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