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

Anna Marlene Schmid, Agnieszka Razim, Magdalena Wysmołek, Daniela Kerekes, Melissa Haunstetter, Paul Kohl, Georgii Brazhnikov, Nora Geissler, Michael Thaler, Eliška Krčmářová, Martin Šindelář, Tamara Weinmayer, Jiří Hrdý, Katy Schmidt, Peter Nejsum, Bradley Whitehead, Johan Palmfeldt, Stefan Schild, Aleksandra Inić-Kanada, Ursula WiedermannIrma Schabussova*

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

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 offers a non-invasive and convenient delivery method. This route bypasses the gastrointestinal tract and provides direct access to the airways, which are the target of asthma prevention. G- bacteria such as E. coli O83 release outer membrane vesicles (OMVs) to communicate with the environment. Here we investigate whether intranasally administered E. coli O83 OMVs (EcO83-OMVs) can reduce allergic airway inflammation in mice. Methods: EcO83-OMVs were isolated by ultracentrifugation and characterised 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 ovalbumin-induced 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 induced the production of pro- and anti-inflammatory cytokines in splenocytes and BMDCs. Intranasal administration of EcO83-OMVs inhibited airway hyperresponsiveness, and decreased airway eosinophilia, Th2 cytokine production and mucus secretion. Conclusions: 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 the prophylactic treatment of allergy. Graphical Abstract: [Figure not available: see fulltext.] [MediaObject not available: see fulltext.].

Original languageEnglish
Article number297
JournalCell Communication and Signaling
Volume21
Issue1
Number of pages17
ISSN1478-811X
DOIs
Publication statusPublished - Dec 2023

Keywords

  • Allergic airway inflammation
  • Extracellular vesicles
  • Microbiota and innate immunity
  • Nasal route of administration
  • Outer membrane vesicles

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