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从猪的骨骼肌和中枢神经系统获取的猪带绦虫囊尾蚴的定量多重蛋白质组学研究。

Quantitative multiplexed proteomics of Taenia solium cysts obtained from the skeletal muscle and central nervous system of pigs.

作者信息

Navarrete-Perea José, Isasa Marta, Paulo Joao A, Corral-Corral Ricardo, Flores-Bautista Jeanette, Hernández-Téllez Beatriz, Bobes Raúl J, Fragoso Gladis, Sciutto Edda, Soberón Xavier, Gygi Steven P, Laclette Juan P

机构信息

Dept. of Immunology, Institute for Biomedical Research, Universidad Nacional Autónoma de México, Ciudad de México, México.

Dept. of Cell Biology, Harvard Medical School, Boston, Massachusetts, United States of America.

出版信息

PLoS Negl Trop Dis. 2017 Sep 25;11(9):e0005962. doi: 10.1371/journal.pntd.0005962. eCollection 2017 Sep.

Abstract

In human and porcine cysticercosis caused by the tapeworm Taenia solium, the larval stage (cysts) can infest several tissues including the central nervous system (CNS) and the skeletal muscles (SM). The cyst's proteomics changes associated with the tissue localization in the host tissues have been poorly studied. Quantitative multiplexed proteomics has the power to evaluate global proteome changes in response to different conditions. Here, using a TMT-multiplexed strategy we identified and quantified over 4,200 proteins in cysts obtained from the SM and CNS of pigs, of which 891 were host proteins. To our knowledge, this is the most extensive intermixing of host and parasite proteins reported for tapeworm infections.Several antigens in cysticercosis, i.e., GP50, paramyosin and a calcium-binding protein were enriched in skeletal muscle cysts. Our results suggested the occurrence of tissue-enriched antigen that could be useful in the improvement of the immunodiagnosis for cysticercosis. Using several algorithms for epitope detection, we selected 42 highly antigenic proteins enriched for each tissue localization of the cysts. Taking into account the fold changes and the antigen/epitope contents, we selected 10 proteins and produced synthetic peptides from the best epitopes. Nine peptides were recognized by serum antibodies of cysticercotic pigs, suggesting that those peptides are antigens. Mixtures of peptides derived from SM and CNS cysts yielded better results than mixtures of peptides derived from a single tissue location, however the identification of the 'optimal' tissue-enriched antigens remains to be discovered. Through machine learning technologies, we determined that a reliable immunodiagnostic test for porcine cysticercosis required at least five different antigenic determinants.

摘要

在由猪带绦虫引起的人和猪囊尾蚴病中,幼虫阶段(囊肿)可侵袭包括中枢神经系统(CNS)和骨骼肌(SM)在内的多种组织。与囊肿在宿主组织中的组织定位相关的蛋白质组学变化研究较少。定量多重蛋白质组学有能力评估在不同条件下的整体蛋白质组变化。在此,我们使用TMT多重策略,鉴定并定量了从猪的骨骼肌和中枢神经系统获得的囊肿中的4200多种蛋白质,其中891种是宿主蛋白。据我们所知,这是绦虫感染中报道的宿主和寄生虫蛋白最广泛的混合情况。囊尾蚴病中的几种抗原,即GP50、副肌球蛋白和一种钙结合蛋白,在骨骼肌囊肿中富集。我们的结果表明存在组织富集抗原,这可能有助于改善囊尾蚴病的免疫诊断。使用几种表位检测算法,我们为囊肿的每个组织定位选择了42种高度抗原性的蛋白质。考虑到倍数变化和抗原/表位含量,我们选择了10种蛋白质,并从最佳表位中制备了合成肽。九种肽被囊尾蚴病猪的血清抗体识别,表明这些肽是抗原。来自骨骼肌和中枢神经系统囊肿的肽混合物比来自单个组织位置的肽混合物产生更好的结果,然而“最佳”组织富集抗原的鉴定仍有待发现。通过机器学习技术,我们确定猪囊尾蚴病的可靠免疫诊断测试至少需要五个不同的抗原决定簇。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234f/5634658/1def19592f2d/pntd.0005962.g009.jpg

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