Continuous in vitro propagation and differentiation of cultures of the intramolluscan stages of the human parasite Schistosoma mansoni

The metazoan parasitic blood flukes, Schistosoma spp., infect over 200 million people worldwide and cause extensive human morbidity and mortality. Research strategies for development of anti-schistosomal agents are impeded by the organism’s complex molluscan–mammalian life cycle, which limits experimental approaches and availability of material. We derived long-term continuously proliferative cultures of Schistosoma mansoni sporocysts capable of generating cercariae in vitro. Cultured organisms retained the ability to parasitize the host, and they exhibited developmental regulation of candidate stage-specific genes in the host-free culture system. Evidence for expression of a reverse transcriptase also was found in the cultured organisms, pointing to this activity as a possible mechanistic contributor to the dynamic relationship between the parasite and its hosts. Continuous in vitro propagation of the asexual sporocyst stage allows isolation of clonally derived parasite populations and provides a means to study schistosomal molecular genetics, metabolism, and evasion of host defenses.

后生动物寄生血吸虫（Schistosoma spp.）在全球范围内感染超2亿人口，造成严重的人体发病与死亡。开发抗血吸虫药物的研究策略受限于该寄生虫复杂的软体动物-哺乳动物宿主生活史，这一特性限制了实验方法的开展与实验材料的获取。我们成功建立了可在体外产生尾蚴的曼氏血吸虫（Schistosoma mansoni）胞蚴长期连续增殖培养体系。培养获得的寄生虫仍保留宿主感染能力，且在无宿主培养体系中展现出候选阶段特异性基因的发育调控特征。研究同时在培养的寄生虫体内检测到逆转录酶（reverse transcriptase）的表达证据，提示该酶活性可能是寄生虫与宿主间动态互作关系的潜在机制之一。无性胞蚴阶段的体外连续培养技术，不仅可用于分离克隆衍生的寄生虫种群，更为研究血吸虫的分子遗传学、代谢机制以及宿主防御逃逸策略提供了有效手段。