Johnston M J G, MacDonald J A, McKay D M
Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada.
Parasitology. 2009 Feb;136(2):125-47. doi: 10.1017/S0031182008005210. Epub 2008 Dec 15.
Infection with parasitic helminths takes a heavy toll on the health and well-being of humans and their domestic livestock, concomitantly resulting in major economic losses. Analyses have consistently revealed bioactive molecules in extracts of helminths or in their excretory/secretory products that modulate the immune response of the host. It is our view that parasitic helminths are an untapped source of immunomodulatory substances that, in pure form, could become new drugs (or models for drug design) to treat disease. Here, we illustrate the range of immunomodulatory molecules in selected parasitic trematodes, cestodes and nematodes, their impact on the immune cells in the host and how the host may recognize these molecules. There are many examples of the partial characterization of helminth-derived immunomodulatory molecules, but these have not yet translated into new drugs, reflecting the difficulty of isolating and fully characterizing proteins, glycoproteins and lipid-based molecules from small amounts of parasite material. However, this should not deter the investigator, since analytical techniques are now being used to accrue considerable structural information on parasite-derived molecules, even when only minute quantities of tissue are available. With the introduction of methodologies to purify and structurally-characterize molecules from small amounts of tissue and the application of high throughput immunological assays, one would predict that an assessment of parasitic helminths will yield a variety of novel drug candidates in the coming years.
感染寄生蠕虫对人类及其家畜的健康和福祉造成了沉重代价，同时也导致了重大的经济损失。分析一致显示，蠕虫提取物或其排泄/分泌产物中存在调节宿主免疫反应的生物活性分子。我们认为，寄生蠕虫是免疫调节物质的未开发来源，其纯形式可成为治疗疾病的新药（或药物设计模型）。在此，我们阐述了选定的寄生吸虫、绦虫和线虫中免疫调节分子的范围、它们对宿主免疫细胞的影响以及宿主如何识别这些分子。有许多关于蠕虫衍生的免疫调节分子部分特征的例子，但这些尚未转化为新药，这反映了从少量寄生虫材料中分离和全面表征蛋白质、糖蛋白和脂质类分子的困难。然而，这不应阻碍研究人员，因为即使只有微量组织可用，现在也正在使用分析技术来积累有关寄生虫衍生分子的大量结构信息。随着从小量组织中纯化和结构表征分子的方法的引入以及高通量免疫测定的应用，可以预测，在未来几年对寄生蠕虫的评估将产生多种新型候选药物。
