Extracellular vesicles of the probiotic bacteria 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 offers a non-invasive and convenient delivery method. This route bypasses...
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| Language: | English |
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BMC
2023-10-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-023-01329-4 |
| _version_ | 1797397906726060032 |
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| author | 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 Wiedermann Irma Schabussova |
| author_facet | 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 Wiedermann Irma Schabussova |
| author_sort | Anna Marlene Schmid |
| collection | DOAJ |
| description | 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 Video Abstract |
| first_indexed | 2024-03-09T01:16:59Z |
| format | Article |
| id | doaj.art-d083c2cca21546f9bff047f761f3090b |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-03-09T01:16:59Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-d083c2cca21546f9bff047f761f3090b2023-12-10T12:26:25ZengBMCCell Communication and Signaling1478-811X2023-10-0121111710.1186/s12964-023-01329-4Extracellular vesicles of the probiotic bacteria E. coli O83 activate innate immunity and prevent allergy in miceAnna Marlene Schmid0Agnieszka Razim1Magdalena Wysmołek2Daniela Kerekes3Melissa Haunstetter4Paul Kohl5Georgii Brazhnikov6Nora Geissler7Michael Thaler8Eliška Krčmářová9Martin Šindelář10Tamara Weinmayer11Jiří Hrdý12Katy Schmidt13Peter Nejsum14Bradley Whitehead15Johan Palmfeldt16Stefan Schild17Aleksandra Inić-Kanada18Ursula Wiedermann19Irma Schabussova20Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of ViennaInstitute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of ViennaInstitute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of ViennaInstitute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of ViennaInstitute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of ViennaInstitute of Molecular Biosciences, Karl-Franzens-UniversityInstitute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of ViennaInstitute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of ViennaInstitute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of ViennaInstitute of Immunology and Microbiology, First Faculty of Medicine, Charles University, and General University HospitalDepartment of Experimental Biology, Faculty of Science, Masaryk UniversityInstitute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of ViennaInstitute of Immunology and Microbiology, First Faculty of Medicine, Charles University, and General University HospitalCore Facility for Cell Imaging and Ultrastructural Research, Faculty of Life Sciences, University of ViennaDepartment of Infectious Diseases, Aarhus University HospitalDepartment of Infectious Diseases, Aarhus University HospitalDepartment of Clinical Medicine, Aarhus UniversityInstitute of Molecular Biosciences, Karl-Franzens-UniversityInstitute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of ViennaInstitute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of ViennaInstitute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of ViennaAbstract 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 Video Abstracthttps://doi.org/10.1186/s12964-023-01329-4Allergic airway inflammationExtracellular vesiclesOuter membrane vesiclesMicrobiota and innate immunityNasal route of administration |
| spellingShingle | 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 Wiedermann Irma Schabussova Extracellular vesicles of the probiotic bacteria E. coli O83 activate innate immunity and prevent allergy in mice Cell Communication and Signaling Allergic airway inflammation Extracellular vesicles Outer membrane vesicles Microbiota and innate immunity Nasal route of administration |
| title | Extracellular vesicles of the probiotic bacteria E. coli O83 activate innate immunity and prevent allergy in mice |
| title_full | Extracellular vesicles of the probiotic bacteria E. coli O83 activate innate immunity and prevent allergy in mice |
| title_fullStr | Extracellular vesicles of the probiotic bacteria E. coli O83 activate innate immunity and prevent allergy in mice |
| title_full_unstemmed | Extracellular vesicles of the probiotic bacteria E. coli O83 activate innate immunity and prevent allergy in mice |
| title_short | Extracellular vesicles of the probiotic bacteria E. coli O83 activate innate immunity and prevent allergy in mice |
| title_sort | extracellular vesicles of the probiotic bacteria e coli o83 activate innate immunity and prevent allergy in mice |
| topic | Allergic airway inflammation Extracellular vesicles Outer membrane vesicles Microbiota and innate immunity Nasal route of administration |
| url | https://doi.org/10.1186/s12964-023-01329-4 |
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