Infection by the Helminth Parasite Fasciola hepatica Requires Rapid Regulation of Metabolic, Virulence, and Invasive Factors to Adjust to Its Mammalian Host.
Infection by the Helminth Parasite Fasciola hepatica Requires Rapid Regulation of Metabolic, Virulence, and Invasive Factors to Adjust to Its Mammalian Host.
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DOI：
10.1074/mcp.ra117.000445
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发表时间：
2018-04
期刊：
影响因子：
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通讯作者：
Dalton JP
中科院分区：
文献类型：
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作者：
Cwiklinski K;Jewhurst H;McVeigh P;Barbour T;Maule AG;Tort J;O'Neill SM;Robinson MW;Donnelly S;Dalton JP
肝片形吸虫寄生虫可以感染多种哺乳动物而不受惩罚。在宿主摄入寄生虫（囊蚴）后，新的脱囊幼虫（NEJ）从包囊中出现，迅速穿透十二指肠壁并迁移到肝脏。成功的感染只需几个小时，并涉及通过宿主大分子，组织和微环境以及免疫系统提出的障碍。在此，转录组和蛋白质组分析离体F。肝吸虫囊蚴和NEJ揭示了为了使寄生虫建立感染而发生的快速和大量的代谢和发育改变。我们发现囊蚴尽管被包裹在包囊中，但代谢活跃，并为感染做好了准备。脱囊后，NEJ消耗重要的能量储存，并迅速调整其代谢途径，以科普新的和日益厌氧的环境。温度升高诱导新生细胞增殖和与生长和发育相关的基因的显著上调。由胃胚层细胞合成的半胱氨酸蛋白酶被分泌以促进入侵和组织降解，并且被膜转运蛋白（例如水通道蛋白）被改变以处理渗透/盐度变化。总NEJ分泌组的主要蛋白质包括蛋白酶、蛋白酶抑制剂和抗氧化剂，以及一系列可能解除宿主先天免疫效应细胞的免疫调节剂。因此，F.肝寄生虫通过加速组织侵入和免疫逃避的快速代谢和生理调节来应对;这些变化促进寄生虫生长、发育和成熟。我们对宿主入侵关键过程的分子分析已经确定了未来预防寄生虫感染的药物和疫苗策略的关键目标。
The parasite Fasciola hepatica infects a broad range of mammals with impunity. Following ingestion of parasites (metacercariae) by the host, newly excysted juveniles (NEJ) emerge from their cysts, rapidly penetrate the duodenal wall and migrate to the liver. Successful infection takes just a few hours and involves negotiating hurdles presented by host macromolecules, tissues and micro-environments, as well as the immune system. Here, transcriptome and proteome analysis of ex vivo F. hepatica metacercariae and NEJ reveal the rapidity and multitude of metabolic and developmental alterations that take place in order for the parasite to establish infection. We found that metacercariae despite being encased in a cyst are metabolically active, and primed for infection. Following excystment, NEJ expend vital energy stores and rapidly adjust their metabolic pathways to cope with their new and increasingly anaerobic environment. Temperature increases induce neoblast proliferation and the remarkable up-regulation of genes associated with growth and development. Cysteine proteases synthesized by gastrodermal cells are secreted to facilitate invasion and tissue degradation, and tegumental transporters, such as aquaporins, are varied to deal with osmotic/salinity changes. Major proteins of the total NEJ secretome include proteases, protease inhibitors and anti-oxidants, and an array of immunomodulators that likely disarm host innate immune effector cells. Thus, the challenges of infection by F. hepatica parasites are met by rapid metabolic and physiological adjustments that expedite tissue invasion and immune evasion; these changes facilitate parasite growth, development and maturation. Our molecular analysis of the critical processes involved in host invasion has identified key targets for future drug and vaccine strategies directed at preventing parasite infection.