| Autor: |
Irma Schabussova, Anna Marlene Schmid, Agnieszka Razim, Magdalena Wysmołek, Daniela Kerekes, Melissa Haunstetter, Paul Kohl, Georgii Brazhnikov, Nora Geissler, Michael Thaler, Eliška Krčmářová, Martin Šindelář, Jiri Hrdy, Katy Schmidt, Peter Nejsum, Bradley Whitehead, Johan Palmfeldt, Stefan Schild, Aleksandra Inic-Kanada, Ursula Wiedermann |
| Rok vydání: |
2023 |
| DOI: |
10.21203/rs.3.rs-2756710/v1 |
| Popis: |
Background:E. coli O83 (Colinfant Newborn) is a Gram-negative (G-) probiotic bacterium used in the clinic. When administered orally, it reduces allergic sensitisation but not allergic asthma. Intranasal administration may be more effective as it reaches the lungs directly. G- bacteria release outer membrane vesicles (OMVs) to communicate with the environment. Here we investigate whether intranasally administered E. coli O83 OMVs (EcO83-OMVs) can reduce allergy in mice. Methods: EcO83-OMVs were isolated by ultracentrifugation and characterised with respect to their number, morphology (shape and size), composition (proteins and lipopolysaccharide; LPS), recognition by innate receptors (using transfected HEK293 cells) and immunomodulatory potential (in naïve splenocytes and bone marrow-derived dendritic cells; BMDCs). Their allergy-preventive effect was investigated in a mouse model of allergic airway inflammation. Results: EcO83-OMVs are spherical nanoparticles with a size of about 110 nm. They contain LPS and protein cargo. We identified a total of 1120 proteins, 136 of which were enriched in OMVs compared to parent bacteria. Proteins from the flagellum dominated. OMVs activated the pattern recognition receptors TLR2/4/5 as well as NOD1 and NOD2. EcO83-OMVs were internalised by epithelial cells and induced the production of pro- and anti-inflammatory cytokines in splenocytes and BMDCs. Intranasal administration of EcO83-OMVs inhibited airway hyperresponsiveness, decreased airway eosinophilia, Th2 cytokine production and mucus secretion. Conclusion: We demonstrate for the first time that intranasally administered OMVs from probiotic G- bacteria have an anti-allergic effect. Our study highlights the advantages of OMVs as a safe platform for prophylactic treatment of allergy. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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