Cortés Alba, Sotillo Javier, Muñoz-Antolí Carla, Molina-Durán Javier, Esteban J Guillermo, Toledo Rafael
Departamento de Parasitología, Facultad de Farmacia, Universidad de Valencia, Burjassot, Valencia, Spain.
Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia.
PLoS Negl Trop Dis. 2017 Jul 17;11(7):e0005773. doi: 10.1371/journal.pntd.0005773. eCollection 2017 Jul.
Helminth infections are among the most prevalent neglected tropical diseases, causing an enormous impact in global health and the socioeconomic growth of developing countries. In this context, the study of helminth biology, with emphasis on host-parasite interactions, appears as a promising approach for developing new tools to prevent and control these infections.
METHODS/PRINCIPAL FINDINGS: The role that antibody responses have on helminth infections is still not well understood. To go in depth into this issue, work on the intestinal helminth Echinostoma caproni (Trematoda: Echinostomatidae) has been undertaken. Adult parasites were recovered from infected mice and cultured in vitro. Double indirect immunofluorescence at increasing culture times was done to show that in vivo-bound surface antibodies become trapped within a layer of excretory/secretory products that covers the parasite. Entrapped antibodies are then degraded by parasite-derived proteases, since protease inhibitors prevent for antibody loss in culture. Electron microscopy and immunogold-labelling of secreted proteins provide evidence that this mechanism is consistent with tegument dynamics and ultrastructure, hence it is feasible to occur in vivo. Secretory vesicles discharge their content to the outside and released products are deposited over the parasite surface enabling antibody trapping.
CONCLUSION/SIGNIFICANCE: At the site of infection, both parasite secretion and antibody binding occur simultaneously and constantly. The continuous entrapment of bound antibodies with newly secreted products may serve to minimize the deleterious effects of the antibody-mediated attack. This mechanism of immune evasion may aid to understand the limited effect that antibody responses have in helminth infections, and may contribute to the basis for vaccine development against these highly prevalent diseases.
蠕虫感染是最普遍的被忽视的热带病之一,对全球健康以及发展中国家的社会经济增长造成了巨大影响。在此背景下,对蠕虫生物学的研究,尤其是宿主-寄生虫相互作用的研究,似乎是开发预防和控制这些感染的新工具的一种有前景的方法。
方法/主要发现:抗体反应在蠕虫感染中所起的作用仍未得到充分理解。为了深入研究这个问题,我们开展了对肠道蠕虫卡氏棘口吸虫(吸虫纲:棘口科)的研究。从感染的小鼠体内获取成虫并进行体外培养。在不同培养时间进行双重间接免疫荧光实验,结果表明体内结合在表面的抗体被困在覆盖寄生虫的一层排泄/分泌产物中。由于蛋白酶抑制剂可防止培养过程中抗体的损失,因此被困的抗体随后会被寄生虫衍生的蛋白酶降解。电子显微镜和对分泌蛋白的免疫金标记提供了证据,表明这一机制与虫体被膜的动态变化和超微结构一致,因此在体内发生是可行的。分泌小泡将其内容物排放到外部,释放的产物沉积在寄生虫表面,从而实现抗体捕获。
结论/意义:在感染部位,寄生虫分泌和抗体结合同时且持续发生。结合的抗体与新分泌产物的持续捕获可能有助于将抗体介导攻击的有害影响降至最低。这种免疫逃避机制可能有助于理解抗体反应在蠕虫感染中的有限作用,并可能为针对这些高度流行疾病的疫苗开发奠定基础。