Acute infection with Strongyloides venezuelensis increases intestine production IL-10, reduces Th1/Th2/Th17 induction in colon and attenuates Dextran Sulfate Sodium-induced colitis in BALB/c mice

Abstract

Helminth infection can reduce the severity of inflammatory bowel disease. However, the modulatory mechanisms elicited by helminth infection are not yet fully understood and vary depending on the experimental model. Herein we evaluated the effect of acute infection of BALB/c mice with Strongyloides venezuelensis on the clinical course of ulcerative colitis induced by Dextran Sulfate Sodium (DSS) treatment of these animals. For the experiments, S. venezuelensis-infected BALB/c mice were treated orally with 4% DSS solution for seven days. As controls, we used untreated S. venezuelensis infected, DSS-treated uninfected, and untreated/uninfected BALB/c mice. During DSS treatment, mice from the different groups were compared with regards to the clinical signs related to the severity of colitis and intestinal inflammation. Mice acutely infected with S. venezulensis and treated with DSS had reduced clinical score, shortening of the colon, and tissue inflammation. Moreover, DSS-treated and infected mice showed reduced IL-4, INF-γ, and IL-17 levels and increase of IL-10 production in the colon and/or in the supernatant of mesenteric lymph nodes cell cultures that resulted in lower eosinophil peroxidase and myeloperoxidase activity in colon homogenates, when compared with DSS-treated uninfected mice. DSS-treated infected mice also preserved the intestine architecture and had normal differentiation of goblet cells and mucus production in the colon mucosa. In conclusion, the data indicate that the clinical improvement reported in DSS-treated infected mice was accompanied by the lower production of Th1/Th2/Th17 pro-inflammatory cytokines, stimulation of IL-10, and induction of mucosal repair mechanisms.

Mucin-2 knockout is a model of intercellular junction defects, mitochondrial damage and ATP depletion in the intestinal epithelium

“…For clinical score evaluation, eight sex-and age-matched animals per experimental group were weighted, appearance and stool samples were checked manually. Clinical score was applied as described by Van der Sluis et al 45 and by Rodrigues et al 90 with modifications. Each parameter was scored as follows:…”

Sequential Changes in the Host Gut Microbiota During Infection With the Intestinal Parasitic Nematode Strongyloides venezuelensis

“…Our results suggested that while the presence of parasite eggs in the feces could be one of the factors that alter the fecal microbiota, other factors are likely to be more important, such as the host immune response or parasite-secreted products. S. venezuelensis infection induces T-helper type 1 (Th1) and Th2 immune responses in the host duodenum and colon (Rodrigues et al, 2018), with Th2 responses in particular causing changes to the intestinal physiology, including increased mucosal permeability, enhanced smooth muscle contractility, and an altered microbiota (Zhao et al, 2003; Artis and Grencis, 2008; Farid et al, 2008; Su et al, 2011). In the present study, we found that Th2-related genes were upregulated in the middle phase of infection.…”

IL-10 and IL-22 in Mucosal Immunity: Driving Protection and Pathology

“…IL-10's protective function has been identified in many colitis models, including the DSS-induced colitis model and the CD45RB hi T cell transfer colitis model, which mimic ulcerative colitis (UC) and Crohn's disease, respectively ( 66 ). IL-10 inhibits IFN-γ production by Th1 cells in mice reconstituted with CD45RB hi CD4 + T cells ( 67 ) and reduces Th17 responses in the DSS model ( 68 , 69 ). As microbiota is involved in the normal physiological status of the colon ( 70 ), the immunomodulatory effects of microbiota-produced short-chain fatty acids (SCFAs) have been examined.…”