Experimental infection with Schistosoma mansoni isolated from the wild rodent Holochilus sciureus shows a low parasite burden but induces high schistosomiasis severity in BALB/c mice.

Wild mammals, especially rodents, can participate in the life cycle of Schistosoma mansoni; however, the impact of these parasite strains on the severity of schistosomiasis remains unclear. The aim of this study was to comparatively evaluate the parasitological and immunopathological alterations induced by an S. mansoni strain isolated from the wild rodent Holochilus sciureus (HS strain) and a parasite strain isolated from a human (LE strain) in experimentally infected mice. Male BALB/c mice were subcutaneously infected with 50 cercariae/mouse of either the HS or the LE strain and were evaluated for 12 weeks. In the experimental groups, the parasite burden was estimated by worm and egg (feces and tissues) count, and immunopathological alterations were evaluated in the liver and intestines. Compared to experimental infection with the LE parasite strain, HS-infected mice showed reduced number of parasite worms but higher fecundity rate, significant reduction in IL-5, IL-10 and IL-13 concentrations, lower EPO-activity in liver homogenate and higher concentrations of TNF-α, IFN-γ, IL-12 and IL-17 in the small intestine homogenate. Moreover, HS infection resulted in higher concentrations of NO end-products in both the liver and intestine, suggesting a predominance of the Th1/Th17 immune response. HS-infected mice also showed higher plasma transaminase levels, formed larger granulomas, and had a higher mortality rate in comparison with LE-infected mice. Data indicate that BALB/c mice infected with the HS strain of S. mansoni showed reduced susceptibility to the parasite but stronger tissue inflammation and high disease severity.

Eosinophils participate in modulation of liver immune response and tissue damage induced by Schistosoma mansoni infection in 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-ß 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.

Strongyloides venezuelensis-infection alters the profile of cytokines and liver inflammation in mice co-infected with Schistosoma mansoni.

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.