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Schistosomiasis mansoni is a major health problem, mainly occurring in developing countries. A large proportion of infected individuals suffers from motility-related gastrointestinal problems. In the present study, the diffuse inflammatory response in the small bowel wall, as compared to the egg-induced granulomatous inflammation, was investigated. For this purpose, OF1 mice infected with Schistosoma mansoni 8-16 weeks prior to the experiment, and uninfected control mice were studied. The ileum showed both a diffuse mucosal inflammation as well as a granulomatous reaction. The diffuse mucosal inflammation caused an increase in the thickness of the mucosa, with blunting of the villi. A significant, transient increase of thickness of the muscularis propria after 12 weeks of infection was noted. There was an infection-related mast cell infiltrate in the muscularis propria, consisting of formalin fixation-insensitive connective tissue mast cells. Ganglionitis of the myenteric plexus was noted. Rarely, ganglia of the myenteric plexus contained apoptotic cells. A general pharmacological set of experiments showed a significant increase in intestinal contractility, both to exogenously administered, as well as to endogenously released neurotransmitters. Our results demonstrate that S. mansoni infection in the mouse ileum leads to diffuse specific enteric inflammation that is associated with an enhanced response to contractile agents.

Smoothelin-A is essential for functional contractility of intestinal smooth muscle. Hampered intestinal transit in smoothelin-A/B knockout mice causes obstruction, starvation, and, ultimately, premature death. The pathology of mice lacking smoothelin-A is reminiscent of that seen in patients with chronic intestinal pseudo-obstruction.

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Background & Aims Nonalcoholic steatohepatitis (NASH) is a multisystem condition, implicating liver and adipose tissue. Although the general involvement of the innate and adaptive immune system has been established, we aimed to define the exact role of the functionally diverse T-cell subsets in NASH pathogenesis through diet reversal and immunologic modulation. Methods Multiple experimental set-ups were used in 8-week-old C57BL/6J mice, including prolonged high-fat high-fructose diet (HFHFD) feeding, diet reversal from HFHFD to control diet, and administration of anti-CD8a and anti–interleukin 17A antibodies. Plasma alanine aminotransferase, glucose, and lipid levels were determined. Liver and adipose tissue were assessed histologically. Cytotoxic T (Tc), regulatory T, T helper (Th) 1, and Th17 cells were characterized in liver and visceral adipose tissue (VAT) via flow cytometry and RNA analysis. Results HFHFD feeding induced the metabolic syndrome and NASH, which coincided with an increase in hepatic Th17, VAT Tc, and VAT Th17 cells, and a decrease in VAT regulatory T cells. Although diet reversal induced a phenotypical metabolic and hepatic normalization, the observed T-cell disruptions persisted. Treatment with anti-CD8a antibodies decreased Tc cell numbers in all investigated tissues and induced a biochemical and histologic attenuation of the HFHFD-induced NASH. Conversely, anti–interleukin 17A antibodies decreased hepatic inflammation without affecting other features of NASH or the metabolic syndrome. Conclusions HFHFD feeding induces important immune disruptions in multiple hepatic and VAT T-cell subsets, refractory to diet reversal. In particular, VAT Tc cells are critically involved in NASH pathogenesis, linking adipose tissue inflammation to liver disease.