Abstract:
Soil-transmitted nematodes (STNs) place a tremendous burden on health and economics worldwide with an estimate of at least 1.5 billion people, or 24% of the population, being infected with at least 1 STN globally. Children and pregnant women carry the heavier pathological burden, and disease caused by the blood-feeding worm in the intestine can result in anaemia and delays in physical and intellectual development. These parasites are capable of infecting and reproducing in various host species, but what determines host specificity remains unanswered. Identifying the molecular determinants of host specificity would provide a crucial breakthrough towards understanding the biology of parasitism and could provide attractive targets for intervention. To investigate specificity mechanisms, members of the hookworm genus Ancylostoma provide a powerful system as they range from strict specialists to generalists. Using transcriptomics, differentially expressed genes (DEGs) in permissive (hamster) and non-permissive (mouse) hosts at different early time points during infection with A. ceylanicum were examined. Analysis of the data has identified unique immune responses in mice, as well as potential permissive signals in hamsters. Specifically, immune pathways associated with resistance to infection are upregulated in the non-permissive host, providing a possible protection mechanism that is absent in the permissive host. Furthermore, unique signatures of host specificity that may inform the parasite that it has invaded a permissive host were identified. These data provide novel insight into the tissue-specific gene expression differences between permissive and non-permissive hosts in response to hookworm infection.
摘要:
土壤传播的线虫(STN)对全世界的健康和经济造成了巨大负担,估计至少有15亿人。或24%的人口,在全球范围内感染至少1个STN。儿童和孕妇承担着较重的病理负担,由肠道中的血液喂养蠕虫引起的疾病会导致贫血和身体和智力发育的延迟。这些寄生虫能够在各种宿主物种中感染和繁殖,但是决定宿主特异性的因素仍然没有答案。确定宿主特异性的分子决定因素将为理解寄生生物学提供重要的突破,并可能为干预提供有吸引力的目标。为了研究特异性机制,钩虫属Ancylostoma的成员提供了强大的系统,从严格的专家到通才。使用转录组学,在用头孢曲霉感染期间的不同早期时间点,检查了许可(仓鼠)和非许可(小鼠)宿主中的差异表达基因(DEGs)。对数据的分析已经确定了小鼠的独特免疫反应,以及仓鼠的潜在许可信号。具体来说,与感染抗性相关的免疫途径在非许可宿主中上调,提供在许可主机中不存在的可能的保护机制。此外,确定了宿主特异性的独特特征,这些特征可能告知寄生虫已入侵许可宿主。这些数据为响应钩虫感染的允许和非允许宿主之间的组织特异性基因表达差异提供了新的见解。