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Immunomodulatory properties of Schistosoma mansoni proteins Sm200 and SmKI-1 in vitro and in a murine model of allergy to the mite Blomia tropicalis.
Molecular Immunology ( IF 3.2 ) Pub Date : 2020-06-13 , DOI: 10.1016/j.molimm.2020.05.011
Camile L S Alves 1 , Leonardo F Santiago 1 , Marina B R Santana 1 , Barbara C P Figueiredo 1 , Suellen B Morais 2 , Sergio C Oliveira 2 , Luis G C Pacheco 1 , Neuza M Alcantara-Neves 1 , Carina S Pinheiro 1
Affiliation  

The prevalence of allergic diseases in Brazil is one of the biggest in the world. Among these pathologies, we highlight asthma as one of the most importance. Asthma is characterized as a chronic inflammatory disease of airways, associated with hyperresponsiveness. Many environmental factors can trigger asthma symptoms, among them house dust mites can stimulate hypersensitivity type I reaction. The most common in house dust mite, in tropical countries, are Dermatophagoides pteronysinus and Blomia tropicalis. Several studies have shown that helminths, especially Schistosoma mansoni, lead to reduction of symptoms of atopy and allergic diseases. Therefore, the present study aims to evaluate the ability of recombinant S. mansoni proteins Sm200, and SmKI-1 to induce immunomodulation in vitro, using peripheral blood mononuclear cells (PBMCs) from atopic and non-atopic individuals, stimulated or not with B. tropicalis extract, and in vivo, in a murine model of allergy to the mite B. tropicalis. As results, we observed that the fragment called rSm200-3 and the protein rSmKI-1 stood out for their immunomodulatory potential, stimulating IL-10 production by human PBMCs in vitro. When these proteins were associated with B. tropicalis extract, it was observed the reduction of the production of the cytokine IL-5, with a statistically significant difference in non-atopic individual’s cells. In vivo, both proteins presented similar results, with a reduction of IL-5 and IL-4 levels in lung homogenates and of serum IgE. SmKI-1 was also able to decrease the levels of EPO in lung homogenates and in BAL. These results showed that both proteins were able to downmodulate Th2 cells on human PBMCs, and in a murine model of allergy. However, SmKI-1 also reduced significantly the levels of EPO in BAL and lungs showing that this protein may be a good candidate to be used as a possible replacement or in conjunction with pharmacotherapy in individuals with unregulated immune response in asthma.



中文翻译:

曼氏血吸虫蛋白Sm200和SmKI-1的免疫调节特性在体外和对热带螨虫过敏的小鼠模型中。

巴西的过敏性疾病患病率是世界上最大的疾病之一。在这些病理中,我们强调哮喘是最重要的疾病之一。哮喘的特征是与高反应性相关的慢性气道炎性疾病。许多环境因素均可引发哮喘症状,其中的屋尘螨可刺激I型超敏反应。在热带国家,最常见的屋尘螨是Dermatophagoides pteronysinusBlomia Tropicalis。多项研究表明,蠕虫,尤其是曼氏血吸虫,可减轻特应性和过敏性疾病的症状。因此,本研究旨在评估重组曼氏沙门氏菌的能力蛋白Sm200和SmKI-1在体外诱导免疫调节,使用来自热带病双歧杆菌提取物刺激或不刺激的异位和非异位个体的外周血单个核细胞(PBMC),以及在体内对小鼠过敏的鼠模型螨B. Tropicalis。结果,我们观察到称为rSm200-3的片段和蛋白rSmKI-1具有突出的免疫调节潜力,可在体外刺激人PBMC产生IL-10 。当这些蛋白质与热带双歧杆菌提取物结合时,观察到细胞因子IL-5的产量减少,非异位个体细胞的统计学差异显着。体内,两种蛋白质均表现出相似的结果,同时降低了肺匀浆和血清IgE中的IL-5和IL-4水平。SmKI-1还能够降低肺匀浆和BAL中的EPO水平。这些结果表明,这两种蛋白都能够在人PBMC和小鼠过敏模型中下调Th2细胞。然而,SmKI-1还可显着降低BAL和肺中EPO的水平,表明该蛋白可能是哮喘患者免疫反应不受调节的个体的替代药物或药物治疗的良好候选者。

更新日期:2020-06-13
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