The Extracellular Vesicles of the Helminth Pathogen, Fasciola hepatica: Biogenesis Pathways and Cargo Molecules Involved in Parasite Pathogenesis.
The Extracellular Vesicles of the Helminth Pathogen, Fasciola hepatica: Biogenesis Pathways and Cargo Molecules Involved in Parasite Pathogenesis.
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DOI：
10.1074/mcp.m115.053934
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发表时间：
2015-12
期刊：
影响因子：
--
通讯作者：
Robinson MW
中科院分区：
文献类型：
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作者：
Cwiklinski K;de la Torre-Escudero E;Trelis M;Bernal D;Dufresne PJ;Brennan GP;O'Neill S;Tort J;Paterson S;Marcilla A;Dalton JP;Robinson MW
寄生虫释放的细胞外囊泡（EVs）在感染的建立和维持中具有重要作用。对成年肝片形吸虫的可溶性和水疱性分泌物的分析已经确定了这种人畜共患寄生虫的总分泌组的明确特征。片形吸虫分泌至少两个ev亚群，它们根据大小、载货分子和从寄生虫释放的位置而不同。较大的ev从寄生胃皮线虫的特化细胞中释放出来，这些细胞含有37 kDa的组织蛋白酶L肽酶的酶原，具有消化功能。较小的外泌体样囊泡群来自被囊合胞体内的多泡体，并携带许多先前描述的可传递到宿主细胞的免疫调节分子。通过将我们的蛋白质组学数据与最近可用的转录组学数据集相结合，我们详细描述了肝梭菌中EV生物发生的途径，并提出小外泌体的生物发生是通过escrt依赖性的MVB在被囊合胞体中形成，然后从顶端质膜脱落。此外，我们发现EV生物发生所需的分子“机制”在寄生虫的哺乳动物发育阶段都有组成性表达。相比之下，包装在EVs内的货物分子受到发育调节，最有可能促进寄生虫在宿主组织中的迁移并抵消宿主的免疫攻击。
Extracellular vesicles (EVs) released by parasites have important roles in establishing and maintaining infection. Analysis of the soluble and vesicular secretions of adult Fasciola hepatica has established a definitive characterization of the total secretome of this zoonotic parasite. Fasciola secretes at least two subpopulations of EVs that differ according to size, cargo molecules and site of release from the parasite. The larger EVs are released from the specialized cells that line the parasite gastrodermus and contain the zymogen of the 37 kDa cathepsin L peptidase that performs a digestive function. The smaller exosome-like vesicle population originate from multivesicular bodies within the tegumental syncytium and carry many previously described immunomodulatory molecules that could be delivered into host cells. By integrating our proteomics data with recently available transcriptomic data sets we have detailed the pathways involved with EV biogenesis in F. hepatica and propose that the small exosome biogenesis occurs via ESCRT-dependent MVB formation in the tegumental syncytium before being shed from the apical plasma membrane. Furthermore, we found that the molecular “machinery” required for EV biogenesis is constitutively expressed across the intramammalian development stages of the parasite. By contrast, the cargo molecules packaged within the EVs are developmentally regulated, most likely to facilitate the parasites migration through host tissue and to counteract host immune attack.