Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
PLoS One. 2013 Jul 2;8(7):e67544. doi: 10.1371/journal.pone.0067544. Print 2013.
One third of the human population is currently infected by one or more species of parasitic helminths. Certain helminths establish long-term chronic infections resulting in a modulation of the host's immune system with attenuated responsiveness to "bystander" antigens such as allergens or vaccines. In this study we investigated whether parasite-derived products suppress the development of allergic inflammation in a mouse model. We show that extract derived from adult male Oesophagostomum dentatum (eMOD) induced Th2 and regulatory responses in BALB/c mice. Stimulation of bone marrow-derived dendritic cells induced production of regulatory cytokines IL-10 and TGF-beta. In a mouse model of birch pollen allergy, co-administration of eMOD with sensitizing allergen Bet v 1 markedly reduced the production of allergen-specific antibodies in serum as well as IgE-dependent basophil degranulation. Furthermore, eMOD prevented the development of airway inflammation, as demonstrated by attenuation of bronchoalveolar lavages eosinophil influx, peribronchial inflammatory infiltrate, and mucus secretion in lungs and IL-4 and IL-5 levels in lung cell cultures. Reduced secretion of Th2-related cytokines by birch pollen-re-stimulated splenocytes and mesenteric lymph node cells was observed in eMOD-treated/sensitized and challenged mice in comparison to sensitized and challenged controls. The suppressive effects of eMOD were heat-stable. Immunization with model antigens in the presence of eMOD reduced production of antibodies to thymus-dependent but not to thymus-independent antigen, suggesting that suppression of the immune responses by eMOD was mediated by interference with antigen presenting cell or T helper cell function but did not directly suppress B cell function. In conclusion, we have shown that eMOD possesses immunomodulatory properties and that heat-stable factors in eMOD are responsible for the dramatic suppression of allergic responses in a mouse model of type I allergy. The identification and characterization of parasite-derived immune-modulating molecules might have potential for designing novel prophylactic/therapeutic strategies for immune-mediated diseases.
目前，全球有三分之一的人口受到一种或多种寄生虫蠕虫的感染。某些蠕虫会建立长期慢性感染，从而导致宿主免疫系统的调节，减弱对“旁观者”抗原（如过敏原或疫苗）的反应。在这项研究中，我们调查了寄生虫衍生产物是否会抑制过敏反应在小鼠模型中的发展。我们发现，从成年雄性 Oesophagostomum dentatum（eMOD）中提取的物质可以在 BALB/c 小鼠中诱导 Th2 和调节反应。刺激骨髓来源的树突状细胞会诱导调节性细胞因子 IL-10 和 TGF-β的产生。在桦树花粉过敏的小鼠模型中，eMOD 与致敏过敏原 Bet v 1 共同给药可显著降低血清中过敏原特异性抗体以及 IgE 依赖性嗜碱性粒细胞脱颗粒的产生。此外，eMOD 可预防气道炎症的发展，表现为支气管肺泡灌洗液嗜酸性粒细胞流入、支气管周围炎症浸润和肺部粘液分泌以及肺细胞培养物中 IL-4 和 IL-5 水平的降低。与致敏和挑战对照组相比，在 eMOD 处理/致敏和挑战的小鼠中，桦树花粉再刺激的脾细胞和肠系膜淋巴结细胞中 Th2 相关细胞因子的分泌减少。在 eMOD 存在的情况下，用模型抗原免疫可降低对胸腺依赖性但不影响对胸腺非依赖性抗原的抗体产生，这表明 eMOD 对免疫反应的抑制作用是通过干扰抗原呈递细胞或辅助性 T 细胞的功能来介导的，但不会直接抑制 B 细胞的功能。总之，我们已经证明 eMOD 具有免疫调节特性，并且 eMOD 中的热稳定因子是导致 I 型过敏小鼠模型中过敏反应显著抑制的原因。鉴定和表征寄生虫衍生的免疫调节分子可能为设计针对免疫介导疾病的新型预防/治疗策略提供了潜力。
