Allergic poly-sensitization affects a large number of allergic patients and poses a great challenge for their treatment. In this study we evaluated the effects of the probiotic Escherichia coli Nissle 1917 (EcN) expressing a birch and grass pollen allergen chimera 'Bet v 1, Phl p 1 and Phl p 5' (EcN-Chim) on allergy prevention after oral or intranasal application in poly-sensitized mice. In contrast to oral application, intranasal pretreatment with EcN-Chim prior to poly-sensitization led to a significant reduction of lung inflammation (eosinophils, IL-5, and IL-13 in bronchoalveolar lavage) along with suppressed levels of allergen-specific serum IgE. The suppression was associated with increased levels of allergen-specific IgA in lungs and serum IgG2a along with increased Foxp3, TGF-β, and IL-10 mRNA in bronchial lymph nodes. In vitro EcN induced high levels of IL-10 and IL-6 in both lung and intestinal epithelial cells. Importantly, using in vivo imaging techniques we demonstrated that intranasally applied EcN do not permanently colonize nose, lung, and gut and this strain might therefore be a safe delivery vector against allergy in humans. In conclusion, our data show that intranasal application of recombinant EcN expressing a multiallergen chimera presents a novel and promising treatment strategy for prevention of allergic poly-sensitization.

中文翻译：

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E. coli Nissle 1917 是一种安全的粘膜递送载体，用于白桦草花粉嵌合体，可防止过敏性多重致敏。

过敏性多致敏影响着大量过敏患者，对其治疗提出了巨大挑战。在这项研究中，我们评估了益生菌大肠杆菌 Nissle 1917 (EcN) 表达桦树和草花粉过敏原嵌合体 'Bet v 1、Phl p 1 和 Phl p 5' (EcN-Chim) 对口服或鼻内过敏预防的影响在多致敏小鼠中的应用。与口服应用相比，在多敏化之前用 EcN-Chim 进行鼻内预处理可显着减少肺部炎症（支气管肺泡灌洗液中的嗜酸性粒细胞、IL-5 和 IL-13），同时抑制过敏原特异性血清 IgE 的水平. 这种抑制与肺中过敏原特异性 IgA 和血清 IgG2a 水平升高以及支气管淋巴结中 Foxp3、TGF-β 和 IL-10 mRNA 水平升高有关。体外 EcN 在肺和肠上皮细胞中诱导高水平的 IL-10 和 IL-6。重要的是，使用体内成像技术，我们证明了鼻内应用的 EcN 不会永久定植在鼻子、肺和肠道中，因此该菌株可能是一种安全的抗过敏传递载体。总之，我们的数据表明，表达多变应原嵌合体的重组 EcN 的鼻内应用为预防变应性多致敏提供了一种新颖且有前途的治疗策略。