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• Strongyloides Strongyloides co-infection in mice did not alter the schistosome parasite burden. • Co-infection resulted in earlier induction of modulatory response. • Simultaneous co-infection stimulated IFN-γ output, increased inflammation and injury. • Co-infection at acute schistosomiasis intensified Th1/Th2/Th17 response and inflammation. • Co-infection alters immune response and liver inflammation induced by schistosomiasis. Human co-infection by helminth species is frequent, but their consequences are mostly unknown. Here, we investigate the impact of Strongyloides venezuelensis co-infection on the immune response, schistosome burden, and the associated pathology of schistosomiasis in mice. Co-infection did not alter the schistosome parasite burden, but reduced the IL-4/IL-10 ratio during acute schistosomiasis, indicating induction of modulatory mechanisms. Simultaneous infection with S. venezuelensis and S. mansoni increased the liver concentration of IFN-γ and altered the Th2/Th1 balance, leading to great infiltration of neutrophils and macrophages, which resulted in larger liver inflammation and increased serum transaminase activity in comparison with mono-infected mice. Mice infected with S. venezuelensis at two and four weeks after S. mansoni infection showed significant increase of Th1/Th2/Th17/Treg cytokines and strong cellular infiltration in the liver in comparison with mono-infected mice. However, only in mice co-infected after two weeks of schistosomiasis, the liver immune response leads to more intense Th2 polarization, increased liver inflammation, and transaminase serum activity. S. venezuelensis co-infection during chronic schistosomiasis did not significantly alter liver inflammation. Therefore, S. venezuelensis co-infection affects the host immune responses and morbidity of schistosomiasis, but the effects largely depend on the stage of the S. mansoni infection. [ABSTRACT FROM AUTHOR]

Proposed model of eosinophil participation in Schistosoma mansoni induced granuloma formation/modulation and disease severity. The absence of eosinophils during S. mansoni infection resulted in significant lower concentration of cytokines from the Th2 profile, such as IL-13, IL-5, IL33 in liver of ∆dblGATA infected mice. There was also reduction in liver concentration of IL-17, and in the regulatory cytokines, IL-10 and TGF- β. In contrast, the liver concentration of TNF- α and INF- γ increased. The changes in liver immune response observed in ∆dblGATA infected mice was accompanied by stronger activation of M1 macrophages, lower expression of COLI and COLII genes and liver content of hydroxyproline, no evident signs of granuloma modulation at chronic schistosomiasis and increase in liver damage, which would contribute to higher mortality rate of ∆dblGATA infected mice. [Display omitted] • Ablation of eosinophils did not alter the S. mansoni load in infected mice. • Infected ΔdblGATA mice displayed reduced liver Th2 and regulatory responses. • S. mansoni infection led to increased liver Th1 response in ΔdblGATA mice. • Infected ΔdblGATA mice displayed larger granulomas and more intense tissue damage. • S. mansoni infection resulted in higher mortality rate in ΔdblGATA mice. The severity of chronic schistosomiasis has been mainly associated with the intensity and extension of the inflammatory response induced by egg-secreted antigens in the host tissue, especially in the liver and intestine. During acute schistosomiasis, eosinophils account for approximately 50% of the cells that compose the liver granulomas; however, the role of this cell-type in the pathology of schistosomiasis remains controversial. In the current study, we compared the parasite burden and liver immunopathological changes during experimental schistosomiasis in wild-type (WT) BALB/c mice and BALB/c mice selectively deficient for the differentiation of eosinophils (ΔdblGATA). Our data demonstrated that the absence of eosinophil differentiation did not alter the S. mansoni load or the liver retention of parasite eggs; however, there were significant changes in the liver immune response profile and tissue damage. S. mansoni infection in ΔdblGATA mice resulted in significantly lower liver concentrations of IL-5, IL-13, IL-33, IL-17, IL-10, and TGF-β and higher concentrations of IFN-γ and TNF-α, as compared to WT mice. The changes in liver immune response observed in infected ΔdblGATA mice were accompanied by lower collagen deposition, but higher liver damage and larger granulomas. Moreover, the absence of eosinophils resulted in a higher mortality rate in mice infected with a high parasite load. Therefore, the data indicated that eosinophils participate in the establishment and/or amplification of liver Th-2 and regulatory response induced by S. mansoni , which is necessary for the balance between liver damage and fibrosis, which in turn is essential for modulating disease severity. [ABSTRACT FROM AUTHOR]

Highlights • S. venezuelensis acute infection reduces severity of DSS-induced colitis. • Nematode infection increased IL-10 production in DSS-treated mice. • The infection reduced Th1/Th2/Th17 cytokine production in DSS-treated mice. • S. venezuelensis induces mucus production and colon repair in DSS-treated 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. [ABSTRACT FROM AUTHOR]