Extracellular vesicles of the probiotic E. coli O83 activate innate
immunity and prevent allergy in mice
Abstract
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.