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RNA-Seq 揭示了致癌性肝吸虫,麝猫后睾吸虫的中间宿主蜗牛体内感染诱导的基因表达变化。

RNA-Seq reveals infection-induced gene expression changes in the snail intermediate host of the carcinogenic liver fluke, Opisthorchis viverrini.

机构信息

Food-borne Parasite Research Group, Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia.

Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia.

出版信息

PLoS Negl Trop Dis. 2014 Mar 27;8(3):e2765. doi: 10.1371/journal.pntd.0002765. eCollection 2014 Mar.

DOI:10.1371/journal.pntd.0002765
PMID:24676090
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3967946/
Abstract

BACKGROUND

Bithynia siamensis goniomphalos is the snail intermediate host of the liver fluke, Opisthorchis viverrini, the leading cause of cholangiocarcinoma (CCA) in the Greater Mekong sub-region of Thailand. Despite the severe public health impact of Opisthorchis-induced CCA, knowledge of the molecular interactions occurring between the parasite and its snail intermediate host is scant. The examination of differences in gene expression profiling between uninfected and O. viverrini-infected B. siamensis goniomphalos could provide clues on fundamental pathways involved in the regulation of snail-parasite interplay.

METHODOLOGY/PRINCIPAL FINDINGS: Using high-throughput (Illumina) sequencing and extensive bioinformatic analyses, we characterized the transcriptomes of uninfected and O. viverrini-infected B. siamensis goniomphalos. Comparative analyses of gene expression profiling allowed the identification of 7,655 differentially expressed genes (DEGs), associated to 43 distinct biological pathways, including pathways associated with immune defense mechanisms against parasites. Amongst the DEGs with immune functions, transcripts encoding distinct proteases displayed the highest down-regulation in Bithynia specimens infected by O. viverrini; conversely, transcription of genes encoding heat-shock proteins and actins was significantly up-regulated in parasite-infected snails when compared to the uninfected counterparts.

CONCLUSIONS/SIGNIFICANCE: The present study lays the foundation for functional studies of genes and gene products potentially involved in immune-molecular mechanisms implicated in the ability of the parasite to successfully colonize its snail intermediate host. The annotated dataset provided herein represents a ready-to-use molecular resource for the discovery of molecular pathways underlying susceptibility and resistance mechanisms of B. siamensis goniomphalos to O. viverrini and for comparative analyses with pulmonate snail intermediate hosts of other platyhelminths including schistosomes.

摘要

背景

湄公河次区域的泰国是肝吸虫(Opisthorchis viverrini)所致胆管癌(CCA)的高发地区,而暹罗圆口螺(Bithynia siamensis goniomphalos)是肝吸虫的螺类中间宿主。尽管肝吸虫感染导致的 CCA 对公共健康造成了严重影响,但人们对寄生虫与其螺类中间宿主之间发生的分子相互作用知之甚少。比较未感染和感染肝吸虫的暹罗圆口螺的基因表达谱差异,可能为研究参与调控螺类-寄生虫相互作用的基本途径提供线索。

方法/主要发现:我们使用高通量(Illumina)测序和广泛的生物信息学分析,对未感染和感染肝吸虫的暹罗圆口螺进行了转录组特征分析。基因表达谱的比较分析鉴定了 7655 个差异表达基因(DEGs),涉及 43 个不同的生物学途径,包括与寄生虫免疫防御机制相关的途径。在具有免疫功能的 DEGs 中,编码不同蛋白酶的转录本在被肝吸虫感染的暹罗圆口螺中表达下调最为明显;相反,与未感染的暹罗圆口螺相比,感染寄生虫的暹罗圆口螺中热休克蛋白和肌动蛋白基因的转录显著上调。

结论/意义:本研究为研究可能参与寄生虫成功定殖螺类中间宿主的免疫分子机制的基因和基因产物的功能研究奠定了基础。本文提供的注释数据集代表了一个现成的分子资源,可用于发现暹罗圆口螺对肝吸虫易感性和抗性的分子途径,并可与其他扁形动物如血吸虫的肺螺类中间宿主进行比较分析。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ae4/3967946/1690256742c7/pntd.0002765.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ae4/3967946/75294fc9f0b4/pntd.0002765.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ae4/3967946/d2086ba672fb/pntd.0002765.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ae4/3967946/1690256742c7/pntd.0002765.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ae4/3967946/75294fc9f0b4/pntd.0002765.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ae4/3967946/d2086ba672fb/pntd.0002765.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ae4/3967946/1690256742c7/pntd.0002765.g003.jpg

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