Japa Ornampai, Hodgkinson Jane E, Emes Richard D, Flynn Robin J
School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, Nottingham, LE12 5RD, UK.
Department of Infection Biology, Institute of Infection and Global Health, University of Liverpool, Liverpool, L3 5RF, UK.
Vet Res. 2015 Mar 11;46:29. doi: 10.1186/s13567-015-0167-2.
The helminth Fasciola hepatica causes fasciolosis throughout the world, a major disease of livestock and an emerging zoonotic disease in humans. Sustainable control mechanisms such as vaccination are urgently required. To discover potential vaccine targets we undertook a genome screen to identify members of the transforming growth factor (TGF) family of proteins. Herein we describe the discovery of three ligands belonging to this superfamily and the cloning and characterisation of an activin/TGF like molecule we term FhTLM. FhTLM has a limited expression pattern both temporally across the parasite stages but also spatially within the worm. Furthermore, a recombinant form of this protein is able to enhance the rate (or magnitude) of multiple developmental processes of the parasite indicating a conserved role for this protein superfamily in the developmental biology of a major trematode parasite. Our study demonstrates for the first time the existence of this protein superfamily within F. hepatica and assigns a function to one of the three identified ligands. Moreover further exploration of this superfamily may yield future targets for diagnostic or vaccination purposes due to its stage restricted expression and functional role.
肝片吸虫这种蠕虫在全球范围内引发肝片吸虫病，这是一种主要的家畜疾病，也是一种在人类中出现的人畜共患病。迫切需要诸如疫苗接种等可持续的控制机制。为了发现潜在的疫苗靶点，我们进行了全基因组筛选，以鉴定转化生长因子（TGF）蛋白家族的成员。在此，我们描述了属于这个超家族的三种配体的发现，以及一种我们称为FhTLM的激活素/TGF样分子的克隆和特性。FhTLM在寄生虫各阶段的时间表达模式有限，在虫体内的空间表达也有限。此外，这种蛋白的重组形式能够提高寄生虫多个发育过程的速率（或幅度），表明这个蛋白超家族在一种主要吸虫寄生虫的发育生物学中具有保守作用。我们的研究首次证明了肝片吸虫中存在这个蛋白超家族，并为鉴定出的三种配体之一赋予了功能。此外，由于其阶段限制性表达和功能作用，对这个超家族的进一步探索可能会产生未来用于诊断或疫苗接种目的的靶点。
