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湄公血吸虫卵蛋白的蛋白质组学和免疫组学分析

Proteomic and immunomic analysis of Schistosoma mekongi egg proteins.

作者信息

Thiangtrongjit Tipparat, Adisakwattana Poom, Limpanont Yanin, Dekumyoy Paron, Nuamtanong Supaporn, Chusongsang Phiraphol, Chusongsang Yupa, Reamtong Onrapak

机构信息

Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand.

Department of Helminthology, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand.

出版信息

Exp Parasitol. 2018 Aug;191:88-96. doi: 10.1016/j.exppara.2018.07.002. Epub 2018 Jul 17.

Abstract

Schistosomiasis remains a global health problem. In the Mekong river basin, approximately 80,000 people are at risk of infection by Schistosoma mekongi. The parasite's eggs become entrapped in the host's organs and induce massive inflammation, contributing to the pathogenesis of schistosomiasis. In addition, egg antigens are important in circumoval precipitin tests (COPTs) and other diagnostic techniques. Little is known regarding the egg proteins of S. mekongi, and so we applied immunoblotting and mass spectrometry-based proteomic approaches to study these proteins and their antigenicity. A total of 360 unique proteins were identified in S. mekongi eggs using proteomic analyses. The major protein components of S. mekongi eggs were classified into several groups by functions, including proteins of unknown function, structural proteins, and regulators of transcription and translation. The most abundant proteins in S. mekongi eggs were antioxidant proteins, potentially reflecting the need to neutralize reactive oxidative species released from host immune cells. Immunomic analyses revealed that only DNA replication factor Cdt1 and heat shock protein 70 overlap between the proteins recognized by sera of infected mice and humans, illustrating the challenges of knowledge transfer from animal models to human patients. Forty-one immunoreactive protein bands were recognized by either mouse or patient sera. Phosphoglycerate kinase, fructose-1,6-bisphosphate aldolase and elongation factor 1 appeared to be interesting immunogens of S. mekongi eggs as these proteins were recognized by polyclonal IgMs and IgGs in patient sera. Our findings provide new information on the protein composition of S. mekongi eggs as well as the beginnings of a S. mekongi immunogen dataset. These data may help us better understand the pathology of schistosomiasis as well as natural antibody responses against S. mekongi egg proteins, both of which may be useful in including S. mekongi to other schistosoma diagnostic, vaccine and immunotherapy development.

摘要

血吸虫病仍然是一个全球性的健康问题。在湄公河流域,约8万人有感染湄公血吸虫的风险。该寄生虫的虫卵会滞留在宿主器官中并引发大量炎症,这是血吸虫病发病机制的一个因素。此外,虫卵抗原在环卵沉淀试验(COPT)及其他诊断技术中很重要。关于湄公血吸虫的虫卵蛋白,我们所知甚少,因此我们应用免疫印迹和基于质谱的蛋白质组学方法来研究这些蛋白及其抗原性。通过蛋白质组学分析,在湄公血吸虫虫卵中总共鉴定出360种独特的蛋白质。湄公血吸虫虫卵的主要蛋白质成分按功能分为几组,包括功能未知的蛋白质、结构蛋白以及转录和翻译调节因子。湄公血吸虫虫卵中最丰富的蛋白质是抗氧化蛋白,这可能反映了中和宿主免疫细胞释放的活性氧化物质的需求。免疫组学分析表明,受感染小鼠和人类血清识别的蛋白质中,只有DNA复制因子Cdt1和热休克蛋白70存在重叠,这说明了从动物模型向人类患者进行知识转化所面临的挑战。小鼠或患者血清识别出41条免疫反应性蛋白条带。磷酸甘油酸激酶、果糖-1,6-二磷酸醛缩酶和延伸因子1似乎是湄公血吸虫虫卵有趣的免疫原,因为这些蛋白质能被患者血清中的多克隆IgM和IgG识别。我们的研究结果提供了关于湄公血吸虫虫卵蛋白质组成的新信息,以及一个湄公血吸虫免疫原数据集的开端。这些数据可能有助于我们更好地理解血吸虫病的病理学以及针对湄公血吸虫虫卵蛋白的天然抗体反应,这两者在将湄公血吸虫纳入其他血吸虫诊断、疫苗和免疫治疗开发中可能都有用。

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