Schistosoma mansoni Venom Allergen Like Proteins Present Differential Allergic Responses in a Murine Model of Airway Inflammation
Schistosoma mansoni Venom Allergen Like Proteins Present Differential Allergic Responses in a Murine Model of Airway Inflammation
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DOI：
10.1371/journal.pntd.0001510
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发表时间：
2012-02-01
影响因子：
3.8
通讯作者：
Leite, Luciana C. C.
中科院分区：
文献类型：
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作者：
Farias, Leonardo Paiva;Rodrigues, Dunia;Leite, Luciana C. C.
背景：曼氏血吸虫毒液过敏原样蛋白 (SmVAL) 是 SCP/TAPS（精子包被蛋白/Tpx-1/Ag5/PR-1/Sc7）蛋白超家族的成员，在宿主与病原体的相互作用中可能很重要。由于其中一些分子的功能分类、表达谱和预测定位，我们和其他人建议将其中一些分子作为潜在的免疫调节剂和候选疫苗。从疫苗的角度来看，问题之一是这些分子的潜在过敏效应。方法/主要发现：在此，我们对假定的分泌蛋白 SmVAL4 和 SmVAL26 进行了表征，并探索了气道炎症的小鼠模型，以研究其潜在的过敏特性。各自的重组蛋白在毕赤酵母系统中获得，纯化的蛋白用于生产特异性抗体。结果表明，SmVAL4 蛋白仅存在于尾蚴阶段，在新转化的血吸虫分泌物中从 0-6 小时开始增加。 SmVAL26仅在卵阶段被鉴定，主要存在于孵化卵的液体中，也存在于培养卵的分泌物中。关于这些蛋白质在气道炎症小鼠模型中的过敏特性的研究，SmVAL4 诱导支气管肺泡灌洗液中细胞总数显着增加，这主要是由于嗜酸性粒细胞和巨噬细胞的增加，这与 IgG1、IgE 和 IL-5 的增加相关，这是典型的过敏性气道炎症反应的特征。被动皮肤过敏 (PCA) 超敏反应检测显示高滴度过敏性 IgG1。此外，在更常规的疫苗试验免疫方案中，rSmVAL4 仍然诱导高水平的 IgG1 和 IgE。 结论：我们的结果表明 SmVAL 家族的成员确实表现出过敏特性；然而，这种情况差异很大，因此在设计血吸虫病疫苗时应予以考虑。此外，小鼠气道炎症模型被证明可用于研究潜在候选疫苗的过敏特性。
Background: The Schistosoma mansoni Venom-Allergen-Like proteins (SmVALs) are members of the SCP/TAPS (Sperm-coating protein/Tpx-1/Ag5/PR-1/Sc7) protein superfamily, which may be important in the host-pathogen interaction. Some of these molecules were suggested by us and others as potential immunomodulators and vaccine candidates, due to their functional classification, expression profile and predicted localization. From a vaccine perspective, one of the concerns is the potential allergic effect of these molecules.Methodology/Principal Findings: Herein, we characterized the putative secreted proteins SmVAL4 and SmVAL26 and explored the mouse model of airway inflammation to investigate their potential allergenic properties. The respective recombinant proteins were obtained in the Pichia pastoris system and the purified proteins used to produce specific antibodies. SmVAL4 protein was revealed to be present only in the cercarial stage, increasing from 0-6 h in the secretions of newly transformed schistosomulum. SmVAL26 was identified only in the egg stage, mainly in the hatched eggs' fluid and also in the secretions of cultured eggs. Concerning the investigation of the allergic properties of these proteins in the mouse model of airway inflammation, SmVAL4 induced a significant increase in total cells in the bronchoalveolar lavage fluid, mostly due to an increase in eosinophils and macrophages, which correlated with increases in IgG1, IgE and IL-5, characterizing a typical allergic airway inflammation response. High titers of anaphylactic IgG1 were revealed by the Passive Cutaneous Anaphylactic (PCA) hypersensitivity assay. Additionally, in a more conventional protocol of immunization for vaccine trials, rSmVAL4 still induced high levels of IgG1 and IgE.Conclusions: Our results suggest that members of the SmVAL family do present allergic properties; however, this varies significantly and therefore should be considered in the design of a schistosomiasis vaccine. Additionally, the murine model of airway inflammation proved to be useful in the investigation of allergic properties of potential vaccine candidates.