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Extracellular Vesicles Produced by the Probiotic Propionibacterium freudenreichii CIRM-BIA 129 Mitigate Inflammation by Modulating the NF-κB Pathway

Extracellular vesicles (EVs) are nanometric spherical structures involved in intercellular communication, whose production is considered to be a widespread phenomenon in living organisms. Bacterial EVs are associated with several processes that include survival, competition, pathogenesis, and immuno...

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Autores principales: Rodovalho, Vinícius de Rezende, da Luz, Brenda Silva Rosa, Rabah, Houem, do Carmo, Fillipe Luiz Rosa, Folador, Edson Luiz, Nicolas, Aurélie, Jardin, Julien, Briard-Bion, Valérie, Blottière, Hervé, Lapaque, Nicolas, Jan, Gwenaël, Le Loir, Yves, de Carvalho Azevedo, Vasco Ariston, Guédon, Eric
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359729/
https://www.ncbi.nlm.nih.gov/pubmed/32733422
http://dx.doi.org/10.3389/fmicb.2020.01544
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author Rodovalho, Vinícius de Rezende
da Luz, Brenda Silva Rosa
Rabah, Houem
do Carmo, Fillipe Luiz Rosa
Folador, Edson Luiz
Nicolas, Aurélie
Jardin, Julien
Briard-Bion, Valérie
Blottière, Hervé
Lapaque, Nicolas
Jan, Gwenaël
Le Loir, Yves
de Carvalho Azevedo, Vasco Ariston
Guédon, Eric
author_facet Rodovalho, Vinícius de Rezende
da Luz, Brenda Silva Rosa
Rabah, Houem
do Carmo, Fillipe Luiz Rosa
Folador, Edson Luiz
Nicolas, Aurélie
Jardin, Julien
Briard-Bion, Valérie
Blottière, Hervé
Lapaque, Nicolas
Jan, Gwenaël
Le Loir, Yves
de Carvalho Azevedo, Vasco Ariston
Guédon, Eric
author_sort Rodovalho, Vinícius de Rezende
collection PubMed
description Extracellular vesicles (EVs) are nanometric spherical structures involved in intercellular communication, whose production is considered to be a widespread phenomenon in living organisms. Bacterial EVs are associated with several processes that include survival, competition, pathogenesis, and immunomodulation. Among probiotic Gram-positive bacteria, some Propionibacterium freudenreichii strains exhibit anti-inflammatory activity, notably via surface proteins such as the surface-layer protein B (SlpB). We have hypothesized that, in addition to surface exposure and secretion of proteins, P. freudenreichii may produce EVs and thus export immunomodulatory proteins to interact with the host. In order to demonstrate their production in this species, EVs were purified from cell-free culture supernatants of the probiotic strain P. freudenreichii CIRM-BIA 129, and their physicochemical characterization, using transmission electron microscopy and nanoparticle tracking analysis (NTA), revealed shapes and sizes typical of EVs. Proteomic characterization showed that EVs contain a broad range of proteins, including immunomodulatory proteins such as SlpB. In silico protein-protein interaction predictions indicated that EV proteins could interact with host proteins, including the immunomodulatory transcription factor NF-κB. This potential interaction has a functional significance because EVs modulate inflammatory responses, as shown by IL-8 release and NF-κB activity, in HT-29 human intestinal epithelial cells. Indeed, EVs displayed an anti-inflammatory effect by modulating the NF-κB pathway; this was dependent on their concentration and on the proinflammatory inducer (LPS-specific). Moreover, while this anti-inflammatory effect partly depended on SlpB, it was not abolished by EV surface proteolysis, suggesting possible intracellular sites of action for EVs. This is the first report on identification of P. freudenreichii-derived EVs, alongside their physicochemical, biochemical and functional characterization. This study has enhanced our understanding of the mechanisms associated with the probiotic activity of P. freudenreichii and identified opportunities to employ bacterial-derived EVs for the development of bioactive products with therapeutic effects.
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spelling pubmed-73597292020-07-29 Extracellular Vesicles Produced by the Probiotic Propionibacterium freudenreichii CIRM-BIA 129 Mitigate Inflammation by Modulating the NF-κB Pathway Rodovalho, Vinícius de Rezende da Luz, Brenda Silva Rosa Rabah, Houem do Carmo, Fillipe Luiz Rosa Folador, Edson Luiz Nicolas, Aurélie Jardin, Julien Briard-Bion, Valérie Blottière, Hervé Lapaque, Nicolas Jan, Gwenaël Le Loir, Yves de Carvalho Azevedo, Vasco Ariston Guédon, Eric Front Microbiol Microbiology Extracellular vesicles (EVs) are nanometric spherical structures involved in intercellular communication, whose production is considered to be a widespread phenomenon in living organisms. Bacterial EVs are associated with several processes that include survival, competition, pathogenesis, and immunomodulation. Among probiotic Gram-positive bacteria, some Propionibacterium freudenreichii strains exhibit anti-inflammatory activity, notably via surface proteins such as the surface-layer protein B (SlpB). We have hypothesized that, in addition to surface exposure and secretion of proteins, P. freudenreichii may produce EVs and thus export immunomodulatory proteins to interact with the host. In order to demonstrate their production in this species, EVs were purified from cell-free culture supernatants of the probiotic strain P. freudenreichii CIRM-BIA 129, and their physicochemical characterization, using transmission electron microscopy and nanoparticle tracking analysis (NTA), revealed shapes and sizes typical of EVs. Proteomic characterization showed that EVs contain a broad range of proteins, including immunomodulatory proteins such as SlpB. In silico protein-protein interaction predictions indicated that EV proteins could interact with host proteins, including the immunomodulatory transcription factor NF-κB. This potential interaction has a functional significance because EVs modulate inflammatory responses, as shown by IL-8 release and NF-κB activity, in HT-29 human intestinal epithelial cells. Indeed, EVs displayed an anti-inflammatory effect by modulating the NF-κB pathway; this was dependent on their concentration and on the proinflammatory inducer (LPS-specific). Moreover, while this anti-inflammatory effect partly depended on SlpB, it was not abolished by EV surface proteolysis, suggesting possible intracellular sites of action for EVs. This is the first report on identification of P. freudenreichii-derived EVs, alongside their physicochemical, biochemical and functional characterization. This study has enhanced our understanding of the mechanisms associated with the probiotic activity of P. freudenreichii and identified opportunities to employ bacterial-derived EVs for the development of bioactive products with therapeutic effects. Frontiers Media S.A. 2020-07-07 /pmc/articles/PMC7359729/ /pubmed/32733422 http://dx.doi.org/10.3389/fmicb.2020.01544 Text en Copyright © 2020 Rodovalho, Luz, Rabah, do Carmo, Folador, Nicolas, Jardin, Briard-Bion, Blottière, Lapaque, Jan, Le Loir, de Carvalho Azevedo and Guédon. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Rodovalho, Vinícius de Rezende
da Luz, Brenda Silva Rosa
Rabah, Houem
do Carmo, Fillipe Luiz Rosa
Folador, Edson Luiz
Nicolas, Aurélie
Jardin, Julien
Briard-Bion, Valérie
Blottière, Hervé
Lapaque, Nicolas
Jan, Gwenaël
Le Loir, Yves
de Carvalho Azevedo, Vasco Ariston
Guédon, Eric
Extracellular Vesicles Produced by the Probiotic Propionibacterium freudenreichii CIRM-BIA 129 Mitigate Inflammation by Modulating the NF-κB Pathway
title Extracellular Vesicles Produced by the Probiotic Propionibacterium freudenreichii CIRM-BIA 129 Mitigate Inflammation by Modulating the NF-κB Pathway
title_full Extracellular Vesicles Produced by the Probiotic Propionibacterium freudenreichii CIRM-BIA 129 Mitigate Inflammation by Modulating the NF-κB Pathway
title_fullStr Extracellular Vesicles Produced by the Probiotic Propionibacterium freudenreichii CIRM-BIA 129 Mitigate Inflammation by Modulating the NF-κB Pathway
title_full_unstemmed Extracellular Vesicles Produced by the Probiotic Propionibacterium freudenreichii CIRM-BIA 129 Mitigate Inflammation by Modulating the NF-κB Pathway
title_short Extracellular Vesicles Produced by the Probiotic Propionibacterium freudenreichii CIRM-BIA 129 Mitigate Inflammation by Modulating the NF-κB Pathway
title_sort extracellular vesicles produced by the probiotic propionibacterium freudenreichii cirm-bia 129 mitigate inflammation by modulating the nf-κb pathway
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359729/
https://www.ncbi.nlm.nih.gov/pubmed/32733422
http://dx.doi.org/10.3389/fmicb.2020.01544
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