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

AM. Schmid, A. Razim, M. Wysmołek, D. Kerekes, M. Haunstetter, P. Kohl, G. Brazhnikov, N. Geissler, M. Thaler, E. Krčmářová, M. Šindelář, T. Weinmayer, J. Hrdý, K. Schmidt, P. Nejsum, B. Whitehead, J. Palmfeldt, S. Schild, A. Inić-Kanada, U....

. 2023 ; 21 (1) : 297. [pub] 20231020

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu audiovizuální média, časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc24001012

Grantová podpora
P 34867 Austrian Science Fund FWF - Austria
P 33073 Austrian Science Fund FWF - Austria
DK W1248-B30 Austrian Science Fund FWF - Austria

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. Video Abstract.

Citace poskytuje Crossref.org

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$a 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. Video Abstract.
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$a Razim, Agnieszka $u Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090, Vienna, Austria $u Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland
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$a Wysmołek, Magdalena $u Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090, Vienna, Austria
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$a Kohl, Paul $u Institute of Molecular Biosciences, Karl-Franzens-University, Graz, Austria
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$a Krčmářová, Eliška $u Institute of Immunology and Microbiology, First Faculty of Medicine, Charles University, and General University Hospital, Prague, Czech Republic
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$a Šindelář, Martin $u Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic
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$a Weinmayer, Tamara $u Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090, Vienna, Austria
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$a Hrdý, Jiří $u Institute of Immunology and Microbiology, First Faculty of Medicine, Charles University, and General University Hospital, Prague, Czech Republic
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$a Schmidt, Katy $u Core Facility for Cell Imaging and Ultrastructural Research, Faculty of Life Sciences, University of Vienna, Vienna, Austria
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$a Nejsum, Peter $u Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark $u Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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