PDF(Pubmed)
Abstract：
Co-evolutionary adaptation of hookworms with their mammalian hosts has been selected for immunoregulatory excretory/secretory (E/S) products. However, it is not known whether, or if so, how host immunological status impacts the secreted profile of hematophagous adult worms. This study interrogated the impact of host Signal transducer and activator of transcription 6 (STAT6) expression during the experimental evolution of hookworms through the sequential passage of the life cycle in either STAT6 deficient or WT C57BL/6 mice. Proteomic analysis of E/S products by LC-MS showed increased abundance of 15 proteins, including myosin-3, related to muscle function, and aconitate hydratase, related to iron homeostasis. However, most E/S proteins (174 of 337 unique identities) were decreased, including those in the Ancylostoma-secreted protein (ASP) category, and metallopeptidases. Several identified proteins are established immune-modulators such as fatty acid-binding protein homologue, cystatin, and acetylcholinesterase. Enrichment analysis of InterPro functional categories showed down-regulation of Cysteine-rich secretory proteins, Antigen 5, and Pathogenesis-related 1 proteins (CAP), Astacin-like metallopeptidase, Glycoside hydrolase, and Transthyretin-like protein groups in STAT6 KO-adapted worms. Taken together, these data indicate that in an environment lacking Type 2 immunity, hookworms alter their secretome by reducing immune evasion proteins- and increasing locomotor- and feeding-associated proteins.
摘要：
钩虫与其哺乳动物宿主的共同进化适应已被选择用于免疫调节排泄/分泌（E/S）产物。然而,不知道是否，或者如果是,宿主免疫状态如何影响食血成虫的分泌谱。这项研究通过STAT6缺陷或WTC57BL/6小鼠的生命周期的顺序传代，询问了钩虫实验进化过程中宿主信号转导和转录激活因子6（STAT6）表达的影响。通过LC-MS对E/S产物进行的蛋白质组学分析显示，15种蛋白质的丰度增加，包括肌球蛋白-3，与肌肉功能有关，和乌头水合酶，与铁稳态有关。然而,大多数E/S蛋白(337个独特身份中的174个)减少，包括Ancylostoma分泌蛋白（ASP）类别，和金属肽酶。几种鉴定的蛋白质是已建立的免疫调节剂，例如脂肪酸结合蛋白同源物，胱抑素,和乙酰胆碱酯酶.InterPro功能类别的富集分析显示富含半胱氨酸的分泌蛋白下调，抗原5和发病相关蛋白1（CAP），Astacin样金属肽酶,糖苷水解酶,STAT6KO适应蠕虫中的运甲状腺素蛋白样蛋白组。一起来看,这些数据表明，在缺乏2型免疫力的环境中，钩虫通过减少免疫逃避蛋白和增加运动和摄食相关蛋白来改变其分泌组。
