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犬弓首蛔虫感染诱导比格犬血浆中的蛋白质组学改变。

Proteomic alterations in the plasma of Beagle dogs induced by Toxocara canis infection.

机构信息

State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu Province 730046, PR China; Hunan Provincial Key Laboratory of Protein Engineering in Animal Vaccines, College of Veterinary Medicine, Hunan Agricultural University, Changsha, Hunan Province 410128, PR China; College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi Province 030801, PR China.

State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu Province 730046, PR China.

出版信息

J Proteomics. 2021 Feb 10;232:104049. doi: 10.1016/j.jprot.2020.104049. Epub 2020 Nov 17.

DOI:10.1016/j.jprot.2020.104049
PMID:33212252
Abstract

Toxocara canis causes ocular larva migrans and visceral larva migrans in humans. Knowledge about the molecular mechanism of T. canis-hosts interaction is limited. The proteomic alterations in the plasma of Beagle dogs induced by T. canis infection were studied by the quantitative mass spectrometry-based data-independent acquisition (DIA). 418, 414 and 411 plasma proteins were identified at 24 h post-infection (hpi), 96 hpi and 36 days post-infection (dpi), including 6, 5 and 23 proteins with differential abundance, respectively. At 24 hpi, the altered proteins, retinoic acid receptor responder protein 2 (RARRES2), WD repeat-containing protein 1 (WDR1), moesin and filamin-A, may participate in pro-inflammatory reaction or promote larvae migration. At 96 hpi, the altered protein C and fibroleukin may maintain the stability of the coagulation system to protect the lung. At 36 dpi, the alterations of C-reactive protein (CRP), ficolin (FCN), complement factor H-related protein 5 (CFHR5) and other complements can affect the three traditional complement system, including the classic pathway, lectin pathway and alternative pathway. These proteins may play important roles in the interaction between T. canis and its definitive hosts. Further study on these altered proteins triggered by T. canis infection may discovery novel therapeutic or diagnostic targets for toxocariasis. SIGNIFICANCE OF THE STUDY: Toxocara canis is one of the globally distributed soil-transmitted helminths, which causes ocular larva migrans and visceral larva migrans in humans and a wide range of warm-blooded animals. T. canis adapts to different microenvironments by resisting and adjusting various biological processes of the hosts. Knowledge about the molecular mechanism of T. canis-hosts interaction is limited. Plasma proteins are good marker for monitoring the occurrence and development of diseases. The proteomic alterations in the plasma of Beagle dogs induced by T. canis infection were studied by the quantitative mass spectrometry-based data-independent acquisition (DIA) in this study. A total of 418, 414 and 411 plasma proteins were identified at 24 h post-infection (hpi), 96 hpi and 36 days post-infection, respectively. Ten protein with differential abundances were validated by using parallel reaction monitoring (PRM). Collectively, our deep proteomic analysis of plasma revealed that proteins alterations were affected by disease development, and proteomic analysis is an ideal method for quantifying changes in circulating factors on a global scale in response to pathophysiological perturbations such as T. canis infection.

摘要

犬弓首蛔虫可引起人体眼幼虫移行症和内脏幼虫移行症。目前对于犬弓首蛔虫与宿主相互作用的分子机制的了解有限。本研究采用基于定量质谱的无依赖数据采集(DIA)技术,研究了犬弓首蛔虫感染诱导的比格犬血浆中的蛋白质组变化。在感染后 24 小时(hpi)、96 hpi 和 36 天(dpi)分别鉴定到 418、414 和 411 种血浆蛋白,分别有 6、5 和 23 种蛋白存在差异丰度。在 24 hpi 时,改变的蛋白包括维甲酸受体应答蛋白 2(RARRES2)、WD 重复蛋白 1(WDR1)、moesin 和细丝蛋白 A,它们可能参与促炎反应或促进幼虫迁移。在 96 hpi 时,改变的蛋白 C 和纤维蛋白原可能维持凝血系统的稳定性以保护肺部。在 36 dpi 时,C 反应蛋白(CRP)、ficolin(FCN)、补体因子 H 相关蛋白 5(CFHR5)和其他补体的改变可影响传统补体系统的三个途径,包括经典途径、凝集素途径和替代途径。这些蛋白可能在犬弓首蛔虫与终宿主的相互作用中发挥重要作用。进一步研究犬弓首蛔虫感染引起的这些改变的蛋白可能为旋毛虫病发现新的治疗或诊断靶点。研究意义:犬弓首蛔虫是一种分布广泛的土壤传播性蠕虫,可引起人体眼幼虫移行症和内脏幼虫移行症以及各种温血动物。犬弓首蛔虫通过抵抗和调节宿主的各种生物过程来适应不同的微环境。目前对于犬弓首蛔虫与宿主相互作用的分子机制的了解有限。血浆蛋白是监测疾病发生和发展的良好标志物。本研究采用基于定量质谱的无依赖数据采集(DIA)技术,研究了犬弓首蛔虫感染诱导的比格犬血浆中的蛋白质组变化。在感染后 24 小时(hpi)、96 hpi 和 36 天(dpi)分别鉴定到 418、414 和 411 种血浆蛋白。通过平行反应监测(PRM)验证了 10 种具有差异丰度的蛋白。综上所述,我们对血浆的深度蛋白质组分析表明,蛋白变化受疾病发展的影响,蛋白质组分析是一种理想的方法,可以定量检测犬弓首蛔虫感染等病理生理扰动下,血浆中循环因子的整体变化。

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