Molecular Helminthology Laboratory, Division of Infectious Diseases, Department of Biomedical Sciences, Cummings School of Veterinary Medicine, Tufts University, Grafton, Massachusetts, United States of America.
PLoS Negl Trop Dis. 2011 Apr 5;5(4):e1011. doi: 10.1371/journal.pntd.0001011.
Schistosomes are parasitic platyhelminths that currently infect over 200 million people globally. The parasites can live for years in a putatively hostile environment - the blood of vertebrates. We have hypothesized that the unusual schistosome tegument (outer-covering) plays a role in protecting parasites in the blood; by impeding host immunological signaling pathways we suggest that tegumental molecules help create an immunologically privileged environment for schistosomes. In this work, we clone and characterize a schistosome alkaline phosphatase (SmAP), a predicted ∼60 kDa glycoprotein that has high sequence conservation with members of the alkaline phosphatase protein family. The SmAP gene is most highly expressed in intravascular parasite life stages. Using immunofluorescence and immuno-electron microscopy, we confirm that SmAP is expressed at the host/parasite interface and in internal tissues. The ability of living parasites to cleave exogenous adenosine monophosphate (AMP) and generate adenosine is very largely abolished when SmAP gene expression is suppressed following RNAi treatment targeting the gene. These results lend support to the hypothesis that schistosome surface enzymes such as SmAP could dampen host immune responses against the parasites by generating immunosuppressants such as adenosine to promote their survival. This notion does not rule out other potential functions for the adenosine generated e.g. in parasite nutrition.
血吸虫是寄生的扁形动物，目前在全球感染了超过 2 亿人。寄生虫可以在一种据称具有敌意的环境——脊椎动物的血液中存活多年。我们假设，血吸虫的特殊表皮（外层覆盖物）在保护血液中的寄生虫方面发挥了作用；通过阻碍宿主的免疫信号通路，我们认为表皮分子有助于为血吸虫创造一个免疫特权环境。在这项工作中，我们克隆并表征了一种血吸虫碱性磷酸酶（SmAP），这是一种预测的约 60 kDa 的糖蛋白，与碱性磷酸酶蛋白家族的成员具有高度的序列保守性。SmAP 基因在血管内寄生虫生活阶段的表达水平最高。通过免疫荧光和免疫电子显微镜，我们证实 SmAP 在宿主/寄生虫界面和内部组织中表达。当针对该基因进行 RNAi 处理以抑制 SmAP 基因表达时，活寄生虫切割外源性单磷酸腺苷（AMP）和生成腺苷的能力大大降低。这些结果支持这样一种假设，即血吸虫表面酶，如 SmAP，通过生成免疫抑制剂（如腺苷）来抑制宿主对寄生虫的免疫反应，从而促进其存活。这一概念并不排除生成的腺苷可能具有其他潜在功能，例如在寄生虫营养中。
