Abstract
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.
Highlights
The burden of allergic diseases has increased significantly in Western countries over the last decades
To assess which TLR signaling pathways were activated by the bacteria, HEK293 cells, with and without stable transfection with TLR2/CD14 or TLR4/MD-2/CD14 were incubated with the three strains
In this study, we have demonstrated that recombinant E. coli Nissle expressing the birch-grass pollen chimera Phl p 5 - Bet v 1Phl p 1 (EcN-Chim) prevents poly-sensitization in mice
Summary
The burden of allergic diseases has increased significantly in Western countries over the last decades. Several factors such as changes in lifestyle, diet, increased hygiene and microbial dysbiosis have been suggested to be responsible for increased allergies.. Around 50–80% of mono-sensitized individuals exhibit poly-sensitization to different allergens with increasing age which significantly affects their quality of life.. The only curative treatment to reduce allergic symptoms in such poly-sensitized patients is subcutaneous or sublingual specific immunotherapy (SIT or SLIT, respectively). It has been shown that poly-sensitized patients are more difficult to successfully treat/tolerize than mono-sensitized individuals by conventional immunotherapy.. Our allergy research has concentrated on the improvement of treatment strategies in poly-sensitized patients. Use of crude extracts of allergens in SIT/SLIT might induce side effects or even mount a certain risk of neosensitization to components in the extract. it has been shown that poly-sensitized patients are more difficult to successfully treat/tolerize than mono-sensitized individuals by conventional immunotherapy. our allergy research has concentrated on the improvement of treatment strategies in poly-sensitized patients.
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