Dataset Information

MicroRNAs Are Involved in the Regulation of Ovary Development in the Pathogenic Blood Fluke Schistosoma japonicum.

ABSTRACT: Schistosomes, blood flukes, are an important global public health concern. Paired adult female schistosomes produce large numbers of eggs that are primarily responsible for the disease pathology and critical for dissemination. Consequently, understanding schistosome sexual maturation and egg production may open novel perspectives for intervening with these processes to prevent clinical symptoms and to interrupt the life-cycle of these blood-flukes. microRNAs (miRNAs) are key regulators of many biological processes including development, cell proliferation, metabolism, and signal transduction. Here, we report on the identification of Schistosoma japonicum miRNAs using small RNA deep sequencing in the key stages of male-female pairing, gametogenesis, and egg production. We identified 38 miRNAs, including 10 previously unknown miRNAs. Eighteen of the miRNAs were differentially expressed between male and female schistosomes and during different stages of sexual maturation. We identified 30 potential target genes for 16 of the S. japonicum miRNAs using antibody-based pull-down assays and bioinformatic analyses. We further validated some of these target genes using either in vitro luciferase assays or in vivo miRNA suppression experiments. Notably, suppression of the female enriched miRNAs bantam and miR-31 led to morphological alteration of ovaries in female schistosomes. These findings uncover key roles for specific miRNAs in schistosome sexual maturation and egg production.

SUBMITTER: Zhu L

PROVIDER: S-EPMC4752461 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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MicroRNAs Are Involved in the Regulation of Ovary Development in the Pathogenic Blood Fluke Schistosoma japonicum.

Zhu Lihui L Zhao Jiangping J Wang Jianbin J Hu Chao C Peng Jinbiao J Luo Rong R Zhou Chunjing C Liu Juntao J Lin Jiaojiao J Jin Youxin Y Davis Richard E RE Cheng Guofeng G

PLoS pathogens 20160212 2

Schistosomes, blood flukes, are an important global public health concern. Paired adult female schistosomes produce large numbers of eggs that are primarily responsible for the disease pathology and critical for dissemination. Consequently, understanding schistosome sexual maturation and egg production may open novel perspectives for intervening with these processes to prevent clinical symptoms and to interrupt the life-cycle of these blood-flukes. microRNAs (miRNAs) are key regulators of many b ...[more]

PMID: 26871705

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Project description:BackgroundDespite successful control efforts in China over the past 60 years, zoonotic schistosomiasis caused by Schistosoma japonicum remains a threat with transmission ongoing and the risk of localised resurgences prompting calls for a novel integrated control strategy, with an anti-schistosome vaccine as a core element. Anti-schistosome vaccine development and immunisation attempts in non-human mammalian host species, intended to interrupt transmission, and utilising various antigen targets, have yielded mixed success, with some studies highlighting variation in schistosome antigen coding genes (ACGs) as possible confounders of vaccine efficacy. Thus, robust selection of target ACGs, including assessment of their genetic diversity and antigenic variability, is paramount. Tetraspanins (TSPs), a family of tegument-surface antigens in schistosomes, interact directly with the host's immune system and are promising vaccine candidates. Here, for the first time to our knowledge, diversity in S. japonicum TSPs (SjTSPs) and the impact of diversifying selection and sequence variation on immunogenicity in these protiens were evaluated.MethodsSjTSP sequences, representing parasite populations from seven provinces across China, were gathered by baiting published short-read NGS data and were analysed using in silico methods to measure sequence variation and selection pressures and predict the impact of selection on variation in antigen protein structure, function and antigenic propensity.ResultsHere, 27 SjTSPs were identified across three subfamilies, highlighting the diversity of TSPs in S. japonicum. Considerable variation was demonstrated for several SjTSPs between geographical regions/provinces, revealing that episodic, diversifying positive selection pressures promote amino acid variation/variability in the large extracellular loop (LEL) domain of certain SjTSPs. Accumulating polymorphisms in the LEL domain of SjTSP-2, -8 and -23 led to altered structural, functional and antibody binding characteristics, which are predicted to impact antibody recognition and possibly blunt the host's ability to respond to infection. Such changes, therefore, appear to represent a mechanism utilised by S. japonicum to evade the host's immune system.ConclusionWhilst the genetic and antigenic geographic variability observed amongst certain SjTSPs could present challenges to vaccine development, here we demonstrate conservation amongst SjTSP-1, -13 and -14, revealing their likely improved utility as efficacious vaccine candidates. Importantly, our data highlight that robust evaluation of vaccine target variability in natural parasite populations should be a prerequisite for anti-schistosome vaccine development.

Project description:Schistosomes are the causative agents of schistosomiasis, one of the most prevalent and serious of the parasitic diseases that currently infects approximately 200 million people worldwide. Schistosome excretory/secretory (ES) proteins have been shown to play important roles in modulating mammalian host immune systems. In our current study, we performed a global proteomics identification of the ES proteins from adult worms of Schistosoma japonicum, one of the three major schistosome species. Our results unambiguously identified 101 proteins, including 53 putatively secreted proteins. By quantitative analysis, we revealed fatty acid-binding protein as a major constituent of the in vitro ES proteome. Strikingly the heat shock proteins HSP70s, HSP90, and HSP97 constituted the largest protein family in the ES proteome, implying a central role for these proteins in immunomodulation in the host-parasite relationship. Other important S. japonicum ES proteins included actins, 14-3-3, aminopeptidase, enolase, and glyceraldehyde-3-phosphate dehydrogenase, some of which have been considered as viable vaccine candidates and therapeutic targets. A comparison with previous studies suggests that 48.5% of S. japonicum ES proteins are common to other parasite ES products, indicating that the molecular mechanisms involved in evading the host immune response may be conserved across different parasites. Interestingly seven host proteins, including antimicrobial protein CAP18, immunoglobulins, and a complement component, were identified among in vitro S. japonicum ES products likely originating from the schistosome tegument or gut, indicating that host innate and acquired immune systems could defend against schistosome invasion. Our present study represents the first attempt at profiling S. japonicum ES proteins, provides an insight into host-parasite interactions, and establishes a resource for the development of diagnostic agents and vaccines for the control of schistosomiasis.

Project description:BACKGROUND: Schistosoma japonicum is one of the remarkable Platyhelminths that are endemic in China and Southeast Asian countries. The parasite is dioecious and can reside inside the host for many years. Rapid reproduction by producing large number of eggs and count-react host anti-parasite responses are the strategies that benefit long term survival of the parasite. Praziquantel is currently the only drug that is effective against the worms. Development of novel antiparasite reagents and immune-prevention measures rely on the deciphering of parasite biology. The decoding of the genomic sequence of the parasite has made it possible to dissect the functions of genes that govern the development of the parasite. In this study, the polyadenylated transcripts from male and female S. japonicum were isolated for deep sequencing and the sequences were systematically analysed. RESULTS: First, the number of genes actively expressed in the two sexes of S. japonicum was similar, but around 50% of genes were biased to either male or female in expression. Secondly, it was, at the first time, found that more than 50% of the coding region of the genome was transcribed from both strands. Among them, 65% of the genes had sense and their cognate antisense transcripts co-expressed, whereas 35% had inverse relationship between sense and antisense transcript abundance. Further, based on gene ontological analysis, more than 2,000 genes were functionally categorized and biological pathways that are differentially functional in male or female parasites were elucidated. CONCLUSIONS: Male and female schistosomal parasites differ in gene expression patterns, many metabolic and biological pathways have been identified in this study and genes differentially expressed in gender specific manner were presented. Importantly, more than 50% of the coding regions of the S. japonicum genome transcribed from both strands, antisense RNA-mediated gene regulation might play a critical role in the parasite biology.

Dataset Information

MicroRNAs Are Involved in the Regulation of Ovary Development in the Pathogenic Blood Fluke Schistosoma japonicum.

Publications

MicroRNAs Are Involved in the Regulation of Ovary Development in the Pathogenic Blood Fluke Schistosoma japonicum.

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