Table_2_ROS are required for the germinative cell proliferation and metacestode larval growth of Echinococcus multilocularis.DOCX

The potentially lethal zoonotic disease alveolar echinococcosis (AE) is caused by the metacestode larval stages of the tapeworm Echinococcus multilocularis. Metacestode growth and proliferation occurs within the inner organs of mammalian hosts, which is associated with complex molecular parasite–host interactions. The host has developed various ways to resist a parasitic infection, and the production of reactive oxygen species (ROS) is one of the most important strategies. Here, we found that scavenging of ROS reduced metacestode larval growth and germinative cell proliferation in in vivo models. Furthermore, using in vitro-cultured metacestode vesicles, we found that increased ROS levels enhanced metacestode growth and germinative cell proliferation, which was achieved by positively activating the ROS-EmERK-EmHIF1α axis. These results indicate that, beside its capacity to damage the parasite, ROS also play critical roles in metacestode growth and germinative cell proliferation. This study suggests that the effects of ROS on parasite may be bidirectional during AE infection, reflecting the parasite’s adaptation to the oxidative stress microenvironment.

具有潜在致死性的人畜共患病泡型棘球蚴病（alveolar echinococcosis, AE）由多房棘球绦虫（Echinococcus multilocularis）的续绦期幼虫阶段引发。续绦期幼虫的生长与增殖发生于哺乳动物宿主的内脏器官中，该过程与复杂的寄生虫-宿主分子互作紧密关联。宿主已演化出多种抵御寄生虫感染的手段，而活性氧（reactive oxygen species, ROS）的产生便是其中最为关键的策略之一。本研究发现，清除活性氧可在体内模型中抑制续绦期幼虫的生长及生发细胞增殖。进一步研究通过体外培养的续绦期囊泡证实，升高的活性氧水平可通过正向激活ROS-EmERK-EmHIF1α信号轴，促进续绦期幼虫的生长与生发细胞增殖。上述结果表明，活性氧除能够对寄生虫造成损伤外，在续绦期幼虫生长及生发细胞增殖过程中同样发挥关键作用。本研究提示，在泡型棘球蚴病感染进程中，活性氧对寄生虫的作用具有双向性，这一现象反映出寄生虫对氧化应激微环境的适应性机制。