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Schistosoma mansoni Infection Is Impacted by Malnutrition.

ABSTRACT: Schistosomiasis remains one of the most important neglected tropical diseases in the world. It mainly affects developing countries, where it often coexists with malnutrition. Despite this, few studies have investigated the relationship between schistosomiasis and malnutrition. Herein, we evaluate the impact of malnutrition on experimental S. mansoni infection. Mice were divided into 5 groups: Control (Ctrl) diet (14% protein and 10% lipids), low-protein 3% (LP 3%), low-protein 8% (LP 8%), low-fat 2.5% (LF 2.5%), and low-fat 5% (LF 5%). Mice were fed with their respective diets and were infected when a difference of approximately 20% in the body weight between mice from any experimental group and mice from the control group was achieved. Nutritional, parasitological, and immunological parameters were assessed either just before infection and/or approximately 50 days later before mice were perfused. Our results showed that the 3% low-protein diet was the only one capable of establishing malnutrition in mice. Mice fed with this diet showed: (i) significant reduction in body weight and serum albumin levels before infection, (ii) decreased levels of all biochemical parameters evaluated before perfusion, (iii) decreased numbers of schistosome eggs trapped in intestines and impaired parasite fecundity, (iv) a delay in the granuloma development with a smaller granuloma area, and (v) reduced levels of IL-4 and IFN-γ in the liver. Our findings demonstrate that low protein supply leads to malnutrition in mice and impacts the cytokine milieu in the liver and granuloma formation. Additionally, the establishment of our murine malnutrition model will enable future studies aiming to better understand the complex relationships between nutrition, immune responses, and infection outcome.

SUBMITTER: Maciel PS

PROVIDER: S-EPMC8017134 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionOffspring of Schistosoma mansoni-infected women in schistosomiasis-endemic areas may be sensitised in-utero. This may influence their immune responsiveness to schistosome infection and schistosomiasis-associated morbidity. Effects of praziquantel treatment of S. mansoni during pregnancy on risk of S. mansoni infection among offspring, and on their immune responsiveness when they become exposed to S. mansoni, are unknown. Here we examined effects of praziquantel treatment of S. mansoni during pregnancy on prevalence of S. mansoni and immune responsiveness among offspring at age five years.MethodsIn a trial in Uganda (ISRCTN32849447, http://www.controlled-trials.com/ISRCTN32849447/elliott), offspring of women treated with praziquantel or placebo during pregnancy were examined for S. mansoni infection and for cytokine and antibody responses to SWA and SEA, as well as for T cell expression of FoxP3, at age five years.ResultsOf the 1343 children examined, 32 (2.4%) had S. mansoni infection at age five years based on a single stool sample. Infection prevalence did not differ between children of treated or untreated mothers. Cytokine (IFN?, IL-5, IL-10 and IL-13) and antibody (IgG1, Ig4 and IgE) responses to SWA and SEA, and FoxP3 expression, were higher among infected than uninfected children. Praziquantel treatment of S. mansoni during pregnancy had no effect on immune responses, with the exception of IL-10 responses to SWA, which was higher in offspring of women that received praziquantel during pregnancy than those who did not.ConclusionWe found no evidence that maternal S. mansoni infection and its treatment during pregnancy influence prevalence and intensity of S. mansoni infection or effector immune response to S. mansoni infection among offspring at age five years, but the observed effects on IL-10 responses to SWA suggest that maternal S. mansoni and its treatment during pregnancy may affect immunoregulatory responsiveness in childhood schistosomiasis. This might have implications for pathogenesis of the disease.

Project description:BackgroundSchistosomiasis is a neglected tropical disease caused by several species of trematode of the genus Schistosoma. The disease affects more than 200 million people in the world and causes up to 280,000 deaths per year, besides having high morbidity due to chronic illness that damages internal organs. Current schistosomiasis control strategies are mainly based on chemotherapy, but many researchers believe that the best long-term strategy to control disease is a combination of drug treatment and immunization with an anti-schistosome vaccine. Among the most promising molecules as vaccine candidates are the proteins present in the tegument and digestive tract of the parasite.Methodology/principal findingsIn this study, we describe for the first time Schistosoma mansoni syntenin (SmSynt) and we evaluate its potential as a recombinant vaccine. We demonstrate by real-time PCR that syntenin is mainly expressed in intravascular life stages (schistosomula and adult worms) of the parasite life cycle and, by confocal microscopy, we localize it in digestive epithelia in adult worms and schistosomula. Administration of siRNAs targeting SmSynt leads to the knock-down of syntenin gene and protein levels, but this has no demonstrable impact on parasite morphology or viability, suggesting that high SmSynt gene expression is not essential for the parasites in vitro. Mice immunization with rSmSynt, formulated with Freund's adjuvant, induces a Th1-type response, as suggested by the production of IFN-? and TNF-? by rSmSynt-stimulated cultured splenocytes. The protective effect conferred by vaccination with rSmSynt was demonstrated by 30-37% reduction of worm burden, 38-43% reduction in the number, and 35-37% reduction in the area, of liver granulomas.Conclusions/significanceOur report is the first characterization of syntenin in Schistosoma mansoni and our data suggest that this protein is a potential candidate for the development of a multi-antigen vaccine to control schistosomiasis.

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Schistosoma mansoni Infection Is Impacted by Malnutrition.

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