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Multiple schistosome and soil-transmitted nematode infections are frequently reported in human populations living in tropical areas of developing countries. In addition to exposure factors, the host immune response plays an important role in helminth control and morbidity in hosts with multiple infections; however, these aspects are difficult to evaluate in human populations. In the current study, female Swiss mice were simultaneously co-infected with Strongyloides venezuelensis and Schistosoma mansoni or infected with St. venezuelensis at 2, 4, or 14 weeks after Sc. mansoni infection. The simultaneously infected mice showed a similar parasite burden for St. venezuelensis compared with mono-infected mice. In contrast, there was a significant reduction of St. venezuelensis burden (primarily during the migration of the larvae) in mice that were previously infected with Sc. mansoni at the acute or chronic phase. Independent of the stage of Sc. mansoni infection, the St. venezuelensis co-infection was capable of inducing IL-4 production in the small intestine, increasing the IgE concentration in the serum and increasing eosinophilia in the lungs and intestine. This result suggests that the nematode infection stimulates local type 2 immune responses independently of the schistosomiasis stage. Moreover, previous Sc. mansoni infection stimulated early granulocyte infiltration in the lungs and trematode-specific IgM and IgG1 production that recognized antigens from St. venezuelensis infective larvae; these immune responses would act in the early control of St. venezuelensis larvae. Our data suggest that the effect of multiple helminth infections on host susceptibility and morbidity largely depends on the species of parasite and the immune response. [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]