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Background & Aims: Hyperplasia of mucin-secreting intestinal goblet cells accompanies a number of enteric infections, including infections by nematode parasites. Nevertheless, the precise role of mucins in host defense in nematode infection is not known. We investigated the role of the mucin (Muc2) in worm expulsion and host immunity in a model of nematode infection., Methods: Resistant (BALB/c, C57BL/6), susceptible (AKR), and Muc2-deficient mouse strains were infected with the nematode, Trichuris muris, and worm expulsion, energy status of the whipworms, changes in mucus/mucins, and inflammatory and immune responses were investigated after infection., Results: The increase in Muc2 production, observed exclusively in resistant mice, correlated with worm expulsion. Moreover, expulsion of the worms from the intestine was significantly delayed in the Muc2-deficient mice. Although a marked impairment in the development of periodic acid Schiff (PAS)-stained intestinal goblet cells was observed in Muc2-deficient mice, as infection progressed a significant increase in the number of PAS-positive goblet cells was observed in these mice. Surprisingly, an increase in Muc5ac, a mucin normally expressed in the airways and stomach, was observed after infection of only the resistant animals. Overall, the mucus barrier in the resistant mice was less permeable than that of susceptible mice. Furthermore, the worms isolated from the resistant mice had a lower energy status., Conclusions: Mucins are an important component of innate defense in enteric infection; this is the first demonstration of the important functional contribution of mucins to host protection from nematode infection., (Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Diet-induced obesity results from increased ingestion of energy-dense food and sedentary lifestyle in genetically susceptible individuals. An environmental factor that may have shaped our energy homeostasis throughout evolution is parasitic nematode infection., Methods: To test the hypothesis that a metabolically "thrifty phenotype" is advantageous during intestinal nematode infection, we compared the responses to Heligmosomoides polygyrus infection between 2 mouse strains: obesity-prone C57Bl/6J vs obesity-resistant SWR/J. Metabolic phenotyping was performed using indirect calorimetry, dual energy x-ray absorptiometry, and magnetic resonance imaging scanning. Gene expression was assessed by quantitative reverse-transcription polymerase chain reaction and immunohistochemistry., Results: Body weight was maintained in both strains during nematode infection via different mechanisms. There was no apparent change in energy expenditure between the strains; however, SWR/J mice exhibited a marked hyperphagia (calorie intake 60% higher than C57Bl/6J) to maintain body weight. The importance of hyperphagia was confirmed by severe weight loss in a group of infected SWR/J mice whose food intake was restricted to that of naïve mice. Furthermore, SWR/J mice expelled nematodes more rapidly than C57Bl/6J mice, an effect related to a T helper cell 2 immune response., Conclusions: C57Bl/6J mice are more energy efficient during parasitic nematode infection, which may explain their ability to tolerate the infection. SWR/J mice, on the other hand, require an increase in food intake to maintain energy stores during nematode infection. In addition, a strong T helper cell 2-mediated immune response that facilitates a prompt clearance of nematode infection in SWR/J mice may have evolved to conserve energy in this strain.

Background & Aims: Studies in inflammatory bowel disease have shown extensive structural abnormalities in the enteric nervous system of inflamed and noninflamed gut; however, functional correlates are lacking. The aim of this study was to determine the effect of colitis on myenteric nerve function at inflamed and noninflamed sites in rat intestine., Methods: Tritiated noradrenaline release was measured from longitudinal muscle myenteric plexus preparations from the distal and transverse colon and terminal ileum of rats with colitis induced by trinitrobenzene sulfonic acid or Trichinella spiralis larvae., Results: As characterized by myeloperoxidase activity and histology, both models induced inflammation restricted to the distal colon. In distal colon in trinitrobenzene sulfonic acid colitis, KCl- or electrical field stimulation-evoked 3H release was suppressed by 56% and 60%, respectively; in T. spiralis-infected rats, the KCl-evoked release was suppressed by 58%. 3H release was also suppressed by similar magnitudes in noninflamed transverse colon and terminal ileum of each model., Conclusions: Experimental distal colitis alters myenteric nerve function in inflamed distal colon and noninflamed gut regions. These changes are independent of the manner in which colitis is induced and provide a basis for the extensive disruption of physiological function observed in inflammatory bowel disease.

Intestinal morphology and fluid and electrolyte transport were examined in a neonatal porcine model of cryptosporidiosis. Sections of jejunum, ileum, and colon were obtained for morphometric analysis on days 3, 6, 9, and 12 postinfection, and in vivo perfusion studies of jejunum and ileum were conducted on days 3 and 4 postinfection. The most severe morphologic lesion was seen in the ileum on day 3, and consisted of villous atrophy, crypt hyperplasia, and cellular infiltration. Villous surface area was reduced from 2.1 +/- 0.4 x 10(5) microns2 in control ileum to 0.8 +/- 0.1 x 10(5) microns2 in infected ileum, a result associated with enterocytes that were fewer in number and reduced in cross-sectional area. Conversely, the number of inflammatory cells in the lamina propria of the villus increased from 456 +/- 116 in control to 1014 +/- 187 in infected villus without a significant change in the volume of the lamina propria. At the height of infection, there was an approximate 1:2 ratio of both organisms and inflammatory cells to villous enterocytes. In contrast, organisms were not observed in the crypts, and the concentration of inflammatory cells in crypt lamina propria was unaltered. Disappearance of organisms and polymorphonuclear cells from the ileum was associated with restoration of normal structure and was complete by day 12. Although organisms were seen in the colon, the general architecture was not severely affected. On days 3 and 4 postinfection, there was a complete impairment of the glucose-stimulated Na and water absorption in both jejunum and ileum of infected pigs; however, absorption of electrolytes and water from a basic Ringer's solution, in the absence of glucose, was not significantly affected. These results are consistent with a malabsorptive diarrheal disease associated with the morphological damage and are very similar to those seen in enteric viral disease in pigs, except that the upper intestine is more severely affected in the latter.

We examined changes in contractility of jejunal longitudinal muscle from rats infected 8 days previously with the enteric parasite Nippostrongylus brasiliensis. In uninfected control rats, carbachol-induced contraction was maximal at 1 microM carbachol. In muscle from infected rats, there was no change in ED50 for carbachol, but contraction induced by 1 microM carbachol was increased greater than 75% over that in control rats. No significant differences were observed in muscarinic receptor binding characteristics in smooth muscle cells from control and infected rats when [3H]QNB was used as radioligand. Contraction induced by 5-hydroxytryptamine was also substantially greater in muscle from infected rats. In control rats, carbachol-induced contraction was largely independent of extracellular Ca2+, whereas in muscle from infected rats, withdrawing extracellular Ca2+ reduced contraction to below control levels. Furthermore, whereas adding nitrendipine in the presence of extracellular Ca2+ had no effect on carbachol-induced contraction in control rats, it significantly inhibited contraction in muscle from infected rats.

In these studies we compared jejunal permeability to two probes--chromium 51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA) (mol wt, 360) and ovalbumin (mol wt, 45,000)--under control conditions, during acute intestinal inflammation, and in response to systemic anaphylaxis. Acute inflammation was produced after infection with Nippostrongylus brasiliensis and rats were studied at day 0 (control), day 4 (early), day 10 (acute), and day 35 (postinfection). At the latter stage, immune rats were also studied during anaphylaxis induced by i.v. N. brasiliensis antigen. In each study, blood and urine were sampled over 5 h after the probes were simultaneously injected into ligated loops in anesthetized rats. In controls, small quantities (less than 0.04% and 0.002% of the administered dose for 51Cr-EDTA and ovalbumin, respectively) appeared in the circulation and plateaued at 1 h. During acute inflammation, the appearance of both probes continued to increase with time. Compared with controls, 5-h values for 51Cr-EDTA and ovalbumin were (a) significantly elevated at day 4 (p less than 0.005), (b) increased approximately 20-fold at day 10 (p less than 0.005 and less than 0.01, respectively), and (c) normal at day 35. Urinary recovery of 51Cr-EDTA followed the same pattern. During anaphylaxis, appearance of the probes in the circulation increased at 1 h to values approximately 10-fold those in controls (p less than 0.001 and less than 0.01, for 51Cr-EDTA and ovalbumin, respectively), and then declined. Urinary recovery of 51Cr-EDTA over 5 h was also significantly increased. We conclude that epithelial barrier function becomes impaired during both acute inflammation and anaphylaxis. In this rat model, gut permeability changes to 51Cr-EDTA reflect gut permeability changes to macromolecular antigens. If similar conditions exist in humans, urinary recovery of 51Cr-EDTA may be useful in monitoring intestinal abnormalities associated with inflammation.