Intestinal Immunity In A Mouse Model Of Postinfectious Irritable Bowel Syndrome

Partâ… Establishment of a mouse model of postinfectious irritable bowel syndromeObjective To observe the changes of visceral sensitivity and colonic muscle strip contractions at different time points after acute Trichinella infectious mice, and to establish a visceral hyperalgesia model imitating patients with post-infectious irritable bowel syndrome (PI-IBS). Methods Mice were infected by Trichinella spiralis (350-400 Trichinella). The weight of the mice at 2,4,8 and 12 weeks was measured. Visceral sensitivity of colorectal distention in mice was accessed by abdominal withdrawal reflex (AWR) at different time points before and after infection. Tissues of jejunum, terminal ileum, proximal colon and distal colon were collected after mice were dead. Histological pathology and inflammation were accessed with HE staining. Contractions of the colonic longitudinal muscle strip were recorded. Results The weight growth rates in 2 and 4-week groups were lower than that in the control group (P<0.05). The rates of 8,12-week groups had no statistical differences with the control groups. In all the groups the intestinal pathologic scores of the 2 weeks group was the highest, the 8,12 weeks groups recovered from the intestinal inflammation, and had no statistical differences with the control groups. At 30,45,60 mmHg, the AWR scores of all the infectious groups were higher than that in the control groups, The perceptual thresholds of all the infectious groups were lower than that in the control groups. Colonic muscle hypercontractility emerged after infection, and was distinguished in the acute infection group. Conclusion The intestinal inflammation in mice dissipated 8 weeks after Trichinella spiralis infection. However, visceral hypersensitivity and colonic muscle hypercontractility remained. Therefore, those mice were suitable for models of visceral hypersensitivity imitating patients with post-infectious irritable bowel syndrome. Partâ…¡Th1/Th2 shift in the intestine of postinfectious irritable bowel syndrome mouseObjective To observe the expression of Thl type cytokine IL-12 and Th2 type cytokine IL-4 in the intestine of the mouse model of post-infectious irritable bowel syndrome (PI-IBS). Methods Mice were infected by Trichinella spiralis (350-400 Trichinella). The weight of the mice was measured every week after infection. Visceral sensitivity of colorectal distention in mice was accessed by abdominal withdrawal reflex (AWR) at 0 and 8 weeks after infection. Tissues of jejunum, terminal ileum, proximal colon and distal colon were collected after mice were dead. Histological pathology and inflammation were accessed with HE staining. The mRNA and protein expressions of IL-12 and IL-4 were examined by RT-PCR and Western blotting, respectively. Results The weight growth rates decreased in 2 weeks acute infectious period (P<0.05). The rates of 8 weeks PI-IBS group had no statistical differences with the control group (P>0.05). Severe inflammation was observed in the intestine of 2 weeks acute infectious period, but after 8 weeks of infection it recovered from the intestinal inflammation, and had no differences with the control group. At 30,45,60 mmHg, the AWR scores of the infectious group was higher than that in the control group, The perceptual thresholds of the infectious group were lower than that in the control group(P<0.05). Increased expression of IL-12 mRNA and protein was observed in the ileocecum and proximal colon of PI-IBS mouse, and decreased expression of IL-4 mRNA and protein was observed in all the parts of intestine of PI-IBS mouse (P<0.05). Conclusion Th1 type cytokine increased but Th2 type cytokine decreased in PI-IBS mouse implied that Th1/Th2 shift may exist in the intestine of post infectious irritable bowel syndrome. Partâ…¢Characteristics of intestinal lamina propria dendritic cells in a mouse model of postinfectious irritable bowel syndromeBackground & Aims Dendritic cell (DC), as an important antigen presenting cell in the intestinal lamina propria, may contribute to intestinal mucosal immune activation in the pathogenesis of postinfectious irritable bowel syndrome (PI-IBS). The aim of this research was to study the phenotypic and functional changes of intestinal lamina propria DCs (LPDCs) in the development of PI-IBS mouse model. Methods Mice infected with T. spiralis underwent abdominal withdrawal reflex (AWR) to evaluate visceral sensitivity. LPDCs were isolated and purified by intestine digestion and magnetic label-based technique. The surface markers of LPDCs were analyzed by flow cytometry. Endocytic activity, mixed lymphocyte reaction (MLR) and chemotaxis were studied. Cytokine production of the LPDCs was determined. Results Intestinal inflammation was serious in acute infection mice, but resolved after 8 weeks infection with sustained visceral hyperalgesia. The surface markers CD86 and MHCII were lower in the acute infection group, but increased in the PI-IBS stage. Enhanced ability of endocytic activity and decreased abilities to attract and stimulate CD4+ T cell proliferation were observed in acute infection group. However, LPDCs in PI-IBS stage showed weakened endocytic ability with enhanced abilities to attract and stimulate CD4+ T cell proliferation. LPDCs secreted more cytokine of IL-4 in acute infection group, while they secreted more cytokines of INF-y and IL-23 in PI-IBS stage. Conclusions The phenotype and function of LPDCs changed in the development of PI-IBS, which induced the maintenance of intestinal mucosal immune activation and might provide a clue for the treatment of the disease.