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Comparative Study of Transcriptome Profiles of Mechanical- and Skin-Transformed Schistosoma mansoni Schistosomula

机译:机械和皮肤转化的曼氏血吸虫血吸虫的转录组谱比较研究

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Schistosome infection begins with the penetration of cercariae through healthy unbroken host skin. This process leads to the transformation of the free-living larvae into obligate parasites called schistosomula. This irreversible transformation, which occurs in as little as two hours, involves casting the cercaria tail and complete remodelling of the surface membrane. At this stage, parasites are vulnerable to host immune attack and oxidative stress. Consequently, the mechanisms by which the parasite recognises and swiftly adapts to the human host are still the subject of many studies, especially in the context of development of intervention strategies against schistosomiasis infection. Because obtaining enough material from in vivo infections is not always feasible for such studies, the transformation process is often mimicked in the laboratory by application of shear pressure to a cercarial sample resulting in mechanically transformed (MT) schistosomula. These parasites share remarkable morphological and biochemical similarity to the naturally transformed counterparts and have been considered a good proxy for parasites undergoing natural infection. Relying on this equivalency, MT schistosomula have been used almost exclusively in high-throughput studies of gene expression, identification of drug targets and identification of effective drugs against schistosomes. However, the transcriptional equivalency between skin-transformed (ST) and MT schistosomula has never been proven. In our approach to compare these two types of schistosomula preparations and to explore differences in gene expression triggered by the presence of a skin barrier, we performed RNA-seq transcriptome profiling of ST and MT schistosomula at 24 hours post transformation. We report that these two very distinct schistosomula preparations differ only in the expression of 38 genes (out of ~11,000), providing convincing evidence to resolve the skin vs. mechanical long-lasting controversy.
机译:血吸虫感染始于尾c通过健康未破裂的宿主皮肤的渗透。这个过程导致自由生活的幼虫转变成专性寄生虫,称为血吸虫。这种不可逆的转变发生在短短的两个小时之内,涉及铸造尾c尾巴和表面膜的完全重塑。在此阶段,寄生虫易受宿主免疫攻击和氧化应激。因此,寄生虫识别并迅速适应人类宿主的机制仍然是许多研究的主题,特别是在针对血吸虫病感染的干预策略的开发中。由于从体内感染中获取足够的材料对于此类研究并不总是可行的,因此在实验室中通常通过对子宫颈样品施加剪切压力来模拟转化过程,从而导致机械转化的(MT)血吸虫。这些寄生虫与天然转化的寄生虫具有明显的形态和生化相似性,并被认为是遭受自然感染的寄生虫的良好替代品。依靠这种等效性,MT血吸虫几乎只用于基因表达的高通量研究,药物靶标的鉴定以及针对血吸虫的有效药物的鉴定。然而,从未证明皮肤转化(ST)和MT血吸虫之间的转录等效性。在我们比较这两种类型的血吸虫制剂和探索由皮肤屏障存在引发的基因表达差异的方法中,我们在转化后24小时对ST和MT血吸虫进行了RNA-seq转录组分析。我们报道这两种截然不同的血吸虫制剂仅在38个基因(约11,000个基因)的表达上有所不同,提供了有说服力的证据来解决皮肤与机械性持久争议。

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