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      Effects of the Environment on Developmental Plasticity and Infection Success of Schistosoma Parasites – An Epigenetic Perspective

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          Abstract

          Evidence of how environmental cues affect the phenotypes of, and compatibility between Schistosoma mansoni and their hosts come from studies in environmental parasitology and research on host diet and chemotherapeutic treatment. Schistosomes deal with a multitude of signals from the water environment as well as cues that come from their hosts, particularly in response to molecules that serve to recognize and destroy them, i.e., those molecules that arise from their hosts’ immune systems. These interactions shape, not only the parasite’s morphology, metabolism and behavior in the short-term, but also their infection success and development into different stage-specific phenotypes later in their life cycle, through the modification of the parasite’s inheritance system. Developmental phenotypic plasticity of S. mansoni is based on epigenetic mechanisms which are also sensitive to environmental cues, but are poorly understood. Here, we argue that specific cues from the environment could lead to changes in parasite development and infectivity, and consequently, environmental signals that come from environmental control measures could be used to influence S. mansoni dynamics and transmission. This approach poses a challenge since epigenetic modification can lead to unexpected and undesired outcomes. However, we suggest that a better understanding of how environmental cues are interpreted by epigenome during schistosome development and host interactions could potentially be applied to control parasite’s virulence. We review evidence about the role of environmental cues on the phenotype of S. mansoni and the compatibility between this parasite and its intermediate and definitive hosts.

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          Most cited references91

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          Schistosomiasis and water resources development: systematic review, meta-analysis, and estimates of people at risk.

          An estimated 779 million people are at risk of schistosomiasis, of whom 106 million (13.6%) live in irrigation schemes or in close proximity to large dam reservoirs. We identified 58 studies that examined the relation between water resources development projects and schistosomiasis, primarily in African settings. We present a systematic literature review and meta-analysis with the following objectives: (1) to update at-risk populations of schistosomiasis and number of people infected in endemic countries, and (2) to quantify the risk of water resources development and management on schistosomiasis. Using 35 datasets from 24 African studies, our meta-analysis showed pooled random risk ratios of 2.4 and 2.6 for urinary and intestinal schistosomiasis, respectively, among people living adjacent to dam reservoirs. The risk ratio estimate for studies evaluating the effect of irrigation on urinary schistosomiasis was in the range 0.02-7.3 (summary estimate 1.1) and that on intestinal schistosomiasis in the range 0.49-23.0 (summary estimate 4.7). Geographic stratification showed important spatial differences, idiosyncratic to the type of water resources development. We conclude that the development and management of water resources is an important risk factor for schistosomiasis, and hence strategies to mitigate negative effects should become integral parts in the planning, implementation, and operation of future water projects.
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            Immunopathogenesis of human schistosomiasis.

            Schistosomiasis continues to be a significant cause of parasitic morbidity and mortality worldwide. This review considers the basic features of the pathology and clinical outcomes of hepatointestinal and genitourinary schistosomiasis, presents an overview of the numerous studies on animal models that have clarified many of the immunopathological features, and provides insight into our current understanding of the immunopathogenesis and genetic control of human schistosomiasis. In murine schistosomiasis, pathology is induced by a CD4(+) Th2 driven granulomatous response directed against schistosome eggs lodged in the host liver. The Th2 cytokines IL-4 and IL-13 drive this response, whereas IL-10, IL13Ralpha2, IFN-gamma and a subset of regulatory T-cells act to limit schistosome induced pathology. A variety of cell types including hepatic stellate cells, alternatively activated macrophages and regulatory T-cells have also been implicated in the pathogenesis of schistosomiasis. Current knowledge suggests the immunopathogenic mechanisms underlying human schistosomiasis are likely to be similar. The review also considers the future development of anti-pathology schistosome vaccines. As fibrosis is an important feature of many other diseases such as Crohn's disease and sarcoidosis, a comprehensive understanding of the cellular and molecular mechanisms involved in schistosomiasis may also ultimately contribute to the development an effective disease intervention strategy for other granulofibrotic diseases.
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              Adult somatic stem cells in the human parasite, Schistosoma mansoni

              Summary Schistosomiasis is among the most prevalent human parasitic diseases, affecting more than 200 million people worldwide 1 . The etiological agents of this disease are trematode flatworms (Schistosoma) that live and lay eggs within the vasculature of the host. These eggs lodge in host tissues, causing inflammatory responses that are the primary cause of morbidity. Because these parasites can live and reproduce within human hosts for decades 2 , elucidating the mechanisms that promote their longevity is of fundamental importance. Although adult pluripotent stem cells, called neoblasts, drive long-term homeostatic tissue maintenance in long-lived free-living flatworms 3,4 (e.g., planarians), and neoblast-like cells have been described in some parasitic tapeworms 5 , little is known about whether similar cell types exist in any trematode species. Here, we describe a population of neoblast-like cells in the trematode Schistosoma mansoni. These cells resemble planarian neoblasts morphologically and share their ability to proliferate and differentiate into derivatives of multiple germ layers. Capitalizing on available genomic resources 6,7 and RNAseq-based gene expression profiling, we find that these schistosome neoblast-like cells express a fibroblast growth factor receptor ortholog. Using RNA interference we demonstrate that this gene is required for the maintenance of these neoblast-like cells. Our observations suggest that adaptation of developmental strategies shared by free-living ancestors to modern-day schistosomes likely contributed to the success of these animals as long-lived obligate parasites. We expect that future studies deciphering the function of these neoblast-like cells will have important implications for understanding the biology of these devastating parasites.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                09 July 2019
                2019
                : 10
                : 1475
                Affiliations
                IHPE UMR 5244, University of Perpignan Via Domitia, CNRS, IFREMER , Perpignan, France
                Author notes

                Edited by: Thiago Almeida Pereira, Stanford University, United States

                Reviewed by: Susanne Sokolow, Stanford University, United States; Adedotun Adesegun Adenusi, University of Lagos, Nigeria; Damilare Olatunji Famakinde contributed to the review of Adedotun Adesegun Adenusi

                *Correspondence: Ronaldo de Carvalho Augusto, ronaldo.augusto@ 123456univ-perp.fr

                This article was submitted to Microbial Immunology, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2019.01475
                6632547
                31354641
                21f10b5d-245c-4ed8-9b1c-4109c335ab0e
                Copyright © 2019 Augusto, Duval and Grunau.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 21 September 2018
                : 13 June 2019
                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 100, Pages: 9, Words: 0
                Funding
                Funded by: Wellcome Trust 10.13039/100004440
                Categories
                Microbiology
                Mini Review

                Microbiology & Virology
                schistosomiasis,environmental cues,inheritance systems,imune response,host-para site interactions

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