The Transcriptome of <em>Trichuris suis</em> – First Molecular Insights into a Parasite with Curative Properties for Key Immune Diseases of Humans

BackgroundIatrogenic infection of humans with Trichuris suis (a parasitic nematode of swine) is being evaluated or promoted as a biological, curative treatment of immune diseases, such as inflammatory bowel disease (IBD) and ulcerative colitis, in humans. Although it is understood that short-term T. suis infection in people with such diseases usually induces a modified Th2-immune response, nothing is known about the molecules in the parasite that induce this response. Methodology/Principal FindingsAs a first step toward filling the gaps in our knowledge of the molecular biology of T. suis, we characterised the transcriptome of the adult stage of this nematode employing next-generation sequencing and bioinformatic techniques. A total of ∼65,000,000 reads were generated and assembled into ∼20,000 contiguous sequences ( = contigs); ∼17,000 peptides were predicted and classified based on homology searches, protein motifs and gene ontology and biological pathway mapping. ConclusionsThese analyses provided interesting insights into a number of molecular groups, particularly predicted excreted/secreted molecules (n = 1,288), likely to be involved in the parasite-host interactions, and also various molecules (n = 120) linked to chemokine, T-cell receptor and TGF-β signalling as well as leukocyte transendothelial migration and natural killer cell-mediated cytotoxicity, which are likely to be immuno-regulatory or -modulatory in the infected host. This information provides a conceptual framework within which to test the immunobiological basis for the curative effect of T. suis infection in humans against some immune diseases. Importantly, the T. suis transcriptome characterised herein provides a curated resource for detailed studies of the immuno-molecular biology of this parasite, and will underpin future genomic and proteomic explorations.背景：将猪鞭虫（Trichuris suis，一种猪寄生线虫）引发的医源性人体感染作为生物性治愈疗法，用于治疗人类炎症性肠病（IBD）、溃疡性结肠炎等免疫疾病的研究与推广工作正在开展。目前已知，罹患此类疾病的患者短期感染猪鞭虫后通常可诱导出修饰后的Th2型免疫应答，但对于该寄生虫中具体哪些分子能够诱导此类应答，目前仍无相关认知。 方法/主要结果：为填补我们在猪鞭虫分子生物学领域认知上的空白，本研究首先采用下一代测序与生物信息学技术，对该线虫成虫的转录组进行了表征分析。本次研究共生成约6500万条测序读段（reads），并将其组装为约2万个连续序列（即重叠群，contigs）；通过同源性搜索、蛋白质基序分析、基因本体（gene ontology）注释及生物学通路映射，共预测得到约17000个肽段并完成分类标注。 结论：上述分析为多个分子类群提供了关键见解，其中尤以预测得到的1288个分泌/排泄（excreted/secreted）分子最为值得关注，这类分子极有可能参与寄生虫-宿主互作过程；此外还鉴定出共计120个与趋化因子、T细胞受体及转化生长因子β（TGF-β）信号通路相关的分子，以及参与白细胞跨内皮迁移、自然杀伤细胞介导的细胞毒性作用的分子，上述分子大概率在感染宿主中发挥免疫调节或免疫调控功能。本研究结果为探究猪鞭虫感染治疗人类部分免疫疾病的免疫生物学基础搭建了理论框架。尤为重要的是，本研究表征得到的猪鞭虫转录组，为该寄生虫免疫分子生物学的深入研究提供了经人工整理注释的标准化资源，同时也将为未来的基因组学与蛋白质组学研究奠定重要基础。