Bacterial EVs as intranasal postbiotics: Detailed characterization and interaction with airway cells
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ABSTRACT: Escherichia coli A0 34/86 (EcO83) is a probiotic bacterium used in newborns to prevent nosocomial infections and diarrhoea. Mechanistically, EcO83 induces the production of pro- and anti-inflammatory cytokines in vitro and in vivo and, when administered intranasally, inhibits allergic airway inflammation in mice by interacting with innate pattern recognition receptors. Despite the proven therapeutic benefit, there is a concern about the use of live bacteria due to the risk of systemic infections and bacterial gene transfer. Therefore, EcO83-derived extracellular vesicles (EcO83-EVs) could represent a safer alternative to live bacteria. However, the exact mechanism of interaction between EV and host remains to be elucidated. Here, we have isolated, purified, and characterised EcO83-EVs following the Minimal Information of Studies of Extracellular Vesicles (MISEV) guidelines. Our ex vivo studies in human nasal epithelial cells showed that EcO83-EVs increased the expression of proteins linked to oxidative stress and inflammation, indicating an effective interaction between EVs and the host cells. Further in vivo studies in mice demonstrated that EcO83-EVs interact with nasal-associated lymphoid tissue, are internalised by airway macrophages, and stimulate neutrophil recruitment in the lung. In vitro analyses revealed that EcO83-EVs activate the NF-κΒ signalling pathway, resulting in the nitric oxide production. Our findings suggest that EcO83-EVs could be an effective and safer postbiotic alternative to live bacteria. Further research is needed to explore the potential of EVs from probiotic bacteria for clinical applications, particularly for mucosal vaccines or targeted immunotherapies.
INSTRUMENT(S): Q Exactive HF
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Epithelial Cell, Cell Culture
SUBMITTER:
Akos Vegvari
LAB HEAD: Akos Vegvari
PROVIDER: PXD052553 | Pride | 2024-11-06
REPOSITORIES: pride
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