Discussion
2,4,6-Trinitrobenzene sulfonic acid (TNBS) and dinitrobenzenesulfonate (DNBS) mouse models are early-stage IBD animal models [18]. The damage caused in these models is highly concentrated, the course of the disease is acute, and the onset is short. Rat and mouse models of intestinal inflammation induced by the oral administration of dextran sulfate sodium (DSS) are also used. The DSS animal model is primarily an injury model, which is primarily used to study the influencing factors of promoting and inhibiting intestinal epithelial healing [19, 20]. In the present study, mice were administered C. rodentium to induce IBD animal models. C. rodentium is an adhesion and shedding pathogen of the family Enterobacteriaceae to which gerbils and mice are susceptible, whereas hamsters and rats are not. This model has been widely used to study the immunoprotective role of E. coli and the mechanism of the host immune response against intestinal pathogens. C. rodentium -induced animal model mice showed obvious inflammatory symptoms in the colon, and the pathological characteristics were consistent with the IBD animal model.
Compared with the TS group, the TS+CR group showed a higher survival rate, reduced intestinal damage, decreased DAI score, and significantly reduced symptoms of intestinal inflammation, indicating that T. spiralis infection could alleviate colitis caused by C. rodentium . This finding is consistent with that observed in other worm infection studies [21, 22].
To better understand how worms suppress the occurrence of immunomodulatory diseases, recent research has focused on the interaction between the Th2- and Th1-type immune responses [23]. Th1 cells primarily secrete IL-2, IFN-γ, IFN-α, and TNF-β, while Th2 cells primarily release IL-4, IL-5, IL-6 and IL-10 [24]. IL-12 plays an important role in Th1 cell-mediated immune response and inflammatory diseases [25]. IL-17 is a pro-inflammatory cytokine produced by T cells and is an early initiating factor of inflammatory responses induced by T cells [26]. In this study, IFN-γ and IL-4, IL-10 were selected as representatives of Th1- and Th2-type cytokines. The number of Th cells was assessed by flow cytometry, and the results showed that T. spiralis infection could reduce the expression of IFN-γ, IL-17 and IL-12 and increase that of IL-4 and IL-10 in colitis mice. These results showed that T. spiralis infection causes a colitis mucosal immune response to switch from a Th1-type response to a protective Th2-type response. ELISA results showed changes in the levels of IgG1 and IgG2a in mouse serum, indicating that the levels of Th2-type cytokines caused by T. spiralis infection have an inhibitory effect on C. rodentium -induced Th1 type inflammation. These reactions reduce the intensity of the Th1-type immune response, thereby alleviating intestinal inflammation, and these results are consistent with the expected experimental results. From another perspective, colitis was also shown to stimulate the switch from a Th2-type immune response induced by T. spiralis larvae infection into a Th1-type immune response, reduce the intensity of the Th2-type immune response, and possibly alleviate the pathological changes attributed to the parasite infection in the body. T. spiralis and C. rodentium interact together to maintain immune balance in mice.
Tregs have a wide range of immunosuppressive effects. By producing regulatory cytokines, these cells maintain the balance of the immune system and prevent the development of autoimmune diseases [27]. Foxp3 is a marker molecule for CD4+CD25+Tregs [28]. The results showed that compared with that observed in the control group, the number of CD4+CD25+Foxp3+Tregs in the spleens and MLNs of mice in the TS group was increased, showing that T. spiralis infection could induce CD4+CD25+Foxp3+Tregs production in mice In contrast, compared with that observed in the TS group, the number of CD4+CD25+Foxp3+Tregs in the spleens and MLNs of mice in the TS+CR group were decreased, showing that C. rodentium infection can affect Tregs in the immune response induced by T. spiralis . The results of the present study are consistent with those of a previous study of worm infections that showed increased levels of Foxp3+Tregs in mouse MLNs and intestinal mucosa lamina propria, inhibiting the mouse colon inflammatory response, as reported by Maloy et al [29].
In summary, the results of the present successfully showed that the effect of T. spiralis intervention on C. rodentium -induced colitis in mice is achieved by regulating the Th1/Th2 type immune response balance of the host.