Duodenal bacterial proteolytic activity determines sensitivity to dietary antigen through protease-activated receptor-2

Microbe-host interactions are generally homeostatic, but when dysfunctional, they can incite food sensitivities and chronic diseases. Celiac disease (CeD) is a food sensitivity characterized by a breakdown of oral tolerance to gluten proteins in genetically predisposed individuals, although the unde...

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Autores principales: Caminero, Alberto, McCarville, Justin L., Galipeau, Heather J., Deraison, Celine, Bernier, Steve P., Constante, Marco, Rolland, Corinne, Meisel, Marlies, Murray, Joseph A., Yu, Xuechen B., Alaedini, Armin, Coombes, Brian K., Bercik, Premysl, Southward, Carolyn M., Ruf, Wolfram, Jabri, Bana, Chirdo, Fernando Gabriel, Casqueiro, Javier, Surette, Michael G., Vergnolle, Nathalie, Verdu, Elena F.
Formato: Articulo
Lenguaje:Inglés
Publicado: 2019
Materias:
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/107005
http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC6416356&blobtype=pdf
Aporte de:
id I19-R120-10915-107005
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Biología
Proteases
Microbe-host interactions
Food sensitivities
spellingShingle Biología
Proteases
Microbe-host interactions
Food sensitivities
Caminero, Alberto
McCarville, Justin L.
Galipeau, Heather J.
Deraison, Celine
Bernier, Steve P.
Constante, Marco
Rolland, Corinne
Meisel, Marlies
Murray, Joseph A.
Yu, Xuechen B.
Alaedini, Armin
Coombes, Brian K.
Bercik, Premysl
Southward, Carolyn M.
Ruf, Wolfram
Jabri, Bana
Chirdo, Fernando Gabriel
Casqueiro, Javier
Surette, Michael G.
Vergnolle, Nathalie
Verdu, Elena F.
Duodenal bacterial proteolytic activity determines sensitivity to dietary antigen through protease-activated receptor-2
topic_facet Biología
Proteases
Microbe-host interactions
Food sensitivities
description Microbe-host interactions are generally homeostatic, but when dysfunctional, they can incite food sensitivities and chronic diseases. Celiac disease (CeD) is a food sensitivity characterized by a breakdown of oral tolerance to gluten proteins in genetically predisposed individuals, although the underlying mechanisms are incompletely understood. Here we show that duodenal biopsies from patients with active CeD have increased proteolytic activity against gluten substrates that correlates with increased Proteobacteria abundance, including Pseudomonas. Using Pseudomonas aeruginosa producing elastase as a model, we show gluten-independent, PAR-2 mediated upregulation of inflammatory pathways in C57BL/6 mice without villus blunting. In mice expressing CeD risk genes, P. aeruginosa elastase synergizes with gluten to induce more severe inflammation that is associated with moderate villus blunting. These results demonstrate that proteases expressed by opportunistic pathogens impact host immune responses that are relevant to the development of food sensitivities, independently of the trigger antigen.
format Articulo
Articulo
author Caminero, Alberto
McCarville, Justin L.
Galipeau, Heather J.
Deraison, Celine
Bernier, Steve P.
Constante, Marco
Rolland, Corinne
Meisel, Marlies
Murray, Joseph A.
Yu, Xuechen B.
Alaedini, Armin
Coombes, Brian K.
Bercik, Premysl
Southward, Carolyn M.
Ruf, Wolfram
Jabri, Bana
Chirdo, Fernando Gabriel
Casqueiro, Javier
Surette, Michael G.
Vergnolle, Nathalie
Verdu, Elena F.
author_facet Caminero, Alberto
McCarville, Justin L.
Galipeau, Heather J.
Deraison, Celine
Bernier, Steve P.
Constante, Marco
Rolland, Corinne
Meisel, Marlies
Murray, Joseph A.
Yu, Xuechen B.
Alaedini, Armin
Coombes, Brian K.
Bercik, Premysl
Southward, Carolyn M.
Ruf, Wolfram
Jabri, Bana
Chirdo, Fernando Gabriel
Casqueiro, Javier
Surette, Michael G.
Vergnolle, Nathalie
Verdu, Elena F.
author_sort Caminero, Alberto
title Duodenal bacterial proteolytic activity determines sensitivity to dietary antigen through protease-activated receptor-2
title_short Duodenal bacterial proteolytic activity determines sensitivity to dietary antigen through protease-activated receptor-2
title_full Duodenal bacterial proteolytic activity determines sensitivity to dietary antigen through protease-activated receptor-2
title_fullStr Duodenal bacterial proteolytic activity determines sensitivity to dietary antigen through protease-activated receptor-2
title_full_unstemmed Duodenal bacterial proteolytic activity determines sensitivity to dietary antigen through protease-activated receptor-2
title_sort duodenal bacterial proteolytic activity determines sensitivity to dietary antigen through protease-activated receptor-2
publishDate 2019
url http://sedici.unlp.edu.ar/handle/10915/107005
http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC6416356&blobtype=pdf
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