关键词: Differential gene expression Fasciola hepatica Intestinal epithelium Newly excysted juveniles RNA-Seq in vitro model

Mesh : Humans Animals Fasciola hepatica / physiology Transcriptome Ecosystem Fascioliasis / veterinary Epithelial Cells

来  源:   DOI:10.1016/j.vetpar.2023.109981

Abstract:
Fasciolosis is a globally widespread trematodiasis with a major economic and veterinary impact. Therefore, this disease is responsible for millions of dollars in losses to the livestock industry, and also constitutes an emerging human health problem in endemic areas. The ubiquitous nature of Fasciola hepatica, the main causative agent, is one of the key factors for the success of fasciolosis. Accordingly, this parasite is able to subsist in a wide variety of ecosystems and hosts, thanks to the development of a plethora of strategies for adaption and immune evasion. Fasciolosis comprises a growing concern due to its high prevalence rates, together with the emergence of strains of the parasite resistant to the treatment of choice (triclabendazole). These facts highlight the importance of developing novel control measures which allow for an effective protection against the disease before F. hepatica settles in a niche inaccessible to the immune system. However, knowledge about the initial phases of the infection, including the migration mechanisms of the parasite and the early innate host response, is still scarce. Recently, our group developed an in vitro host-parasite interaction model that allowed the early events to be unveiled after the first contact between the both actors. This occurs shortly upon ingestion of F. hepatica metacercariae and the emergence of the newly excysted juveniles (FhNEJ) in the host duodenum. Here, we present a transcriptomic analysis of such model using an approach based on RNA sequencing (RNA-Seq), which reveals changes in gene expression related to proteolysis and uptake of metabolites in FhNEJ. Additionally, contact with the parasite triggered changes in host intestinal cells related to pseudogenes expression and host defence mechanisms, including immune response, among others. In sum, these results provide a better understanding of the early stages of fasciolosis at molecular level, and a pool of targets that could be used in future therapeutic strategies against the disease.
摘要:
筋膜虫病是一种全球广泛分布的吸虫病,具有重大的经济和兽医影响。因此,这种疾病给畜牧业造成了数百万美元的损失,也是流行地区正在出现的人类健康问题。肝片吸虫的无处不在,主要病原体,是法西斯成功的关键因素之一。因此,这种寄生虫能够在各种各样的生态系统和宿主中生存,由于大量适应和免疫逃避策略的发展。筋膜病由于其患病率高,引起了越来越多的关注,连同出现的菌株的寄生虫耐药的治疗选择(三苯多唑)。这些事实凸显了开发新的控制措施的重要性,这些措施可以在肝菌定居在免疫系统无法进入的利基中之前有效地预防该疾病。然而,了解感染的初始阶段,包括寄生虫的迁移机制和早期的先天宿主反应,仍然稀缺。最近,我们的研究小组开发了一种体外宿主-寄生虫相互作用模型,该模型允许在两个参与者首次接触后公布早期事件.这发生在摄入肝肝F.cer虫和在宿主十二指肠中出现新的囊虫(FhNEJ)后不久。这里,我们使用基于RNA测序(RNA-Seq)的方法对此类模型进行转录组学分析,这揭示了FhNEJ中与蛋白水解和代谢产物摄取相关的基因表达变化。此外,与寄生虫的接触引发了与假基因表达和宿主防御机制相关的宿主肠细胞的变化,包括免疫反应,在其他人中。总之,这些结果在分子水平上提供了对筋膜病早期阶段的更好理解,以及可用于未来治疗该疾病的靶标库。
公众号