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

Autores
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.
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Caminero, Alberto. Mc Master University; Canadá
Fil: McCarville, Justin L.. Mc Master University; Canadá
Fil: Galipeau, Heather J.. Mc Master University; Canadá
Fil: Deraison, Celine. Université de Toulouse; Francia
Fil: Bernier, Steve P.. Mc Master University; Canadá
Fil: Constante, Marco. Mc Master University; Canadá
Fil: Rolland, Corinne. Université de Toulouse; Francia
Fil: Meisel, Marlies. University of Chicago; Estados Unidos
Fil: Murray, Joseph A.. Mayo Clinic College of Medicine; Estados Unidos
Fil: Yu, Xuechen B.. Columbia University; Estados Unidos
Fil: Alaedini, Armin. Columbia University; Estados Unidos
Fil: Coombes, Brian K.. Mc Master University; Canadá
Fil: Bercik, Premysl. Mc Master University; Canadá
Fil: Southward, Carolyn M.. Mc Master University; Canadá
Fil: Ruf, Wolfram. The Scripps Research Institute; Estados Unidos. Johannes Gutenberg Universitat Mainz; Alemania
Fil: Jabri, Bana. University of Chicago; Estados Unidos
Fil: Chirdo, Fernando Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina
Fil: Casqueiro, Javier. Universidad de León; España
Fil: Surette, Michael G.. Mc Master University; Canadá
Fil: Vergnolle, Nathalie. Université de Toulouse; Francia
Fil: Verdu, Elena F.. Mc Master University; Canadá
Materia
Celiac Dsease
Microbiota
Mucosal Immunity
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/152154
Acceder
id CONICETDig_fe1cf9e0f754e6383fac0c616564dbcc
oai_identifier_str oai:ri.conicet.gov.ar:11336/152154
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Duodenal bacterial proteolytic activity determines sensitivity to dietary antigen through protease-activated receptor-2Caminero, AlbertoMcCarville, Justin L.Galipeau, Heather J.Deraison, CelineBernier, Steve P.Constante, MarcoRolland, CorinneMeisel, MarliesMurray, Joseph A.Yu, Xuechen B.Alaedini, ArminCoombes, Brian K.Bercik, PremyslSouthward, Carolyn M.Ruf, WolframJabri, BanaChirdo, Fernando GabrielCasqueiro, JavierSurette, Michael G.Vergnolle, NathalieVerdu, Elena F.Celiac DseaseMicrobiotaMucosal Immunityhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Microbe-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.Fil: Caminero, Alberto. Mc Master University; CanadáFil: McCarville, Justin L.. Mc Master University; CanadáFil: Galipeau, Heather J.. Mc Master University; CanadáFil: Deraison, Celine. Université de Toulouse; FranciaFil: Bernier, Steve P.. Mc Master University; CanadáFil: Constante, Marco. Mc Master University; CanadáFil: Rolland, Corinne. Université de Toulouse; FranciaFil: Meisel, Marlies. University of Chicago; Estados UnidosFil: Murray, Joseph A.. Mayo Clinic College of Medicine; Estados UnidosFil: Yu, Xuechen B.. Columbia University; Estados UnidosFil: Alaedini, Armin. Columbia University; Estados UnidosFil: Coombes, Brian K.. Mc Master University; CanadáFil: Bercik, Premysl. Mc Master University; CanadáFil: Southward, Carolyn M.. Mc Master University; CanadáFil: Ruf, Wolfram. The Scripps Research Institute; Estados Unidos. Johannes Gutenberg Universitat Mainz; AlemaniaFil: Jabri, Bana. University of Chicago; Estados UnidosFil: Chirdo, Fernando Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Casqueiro, Javier. Universidad de León; EspañaFil: Surette, Michael G.. Mc Master University; CanadáFil: Vergnolle, Nathalie. Université de Toulouse; FranciaFil: Verdu, Elena F.. Mc Master University; CanadáNature Publishing Group2019-03-13info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/152154Caminero, Alberto; McCarville, Justin L.; Galipeau, Heather J.; Deraison, Celine; Bernier, Steve P.; et al.; Duodenal bacterial proteolytic activity determines sensitivity to dietary antigen through protease-activated receptor-2; Nature Publishing Group; Nature Communications; 10; 1; 13-3-2019; 1-142041-1723CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/s41467-019-09037-9info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41467-019-09037-9info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:09:31Zoai:ri.conicet.gov.ar:11336/152154instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:09:31.485CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Duodenal bacterial proteolytic activity determines sensitivity to dietary antigen through protease-activated receptor-2
title Duodenal bacterial proteolytic activity determines sensitivity to dietary antigen through protease-activated receptor-2
spellingShingle Duodenal bacterial proteolytic activity determines sensitivity to dietary antigen through protease-activated receptor-2
Caminero, Alberto
Celiac Dsease
Microbiota
Mucosal Immunity
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
dc.creator.none.fl_str_mv 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 Caminero, Alberto
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_role author
author2 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.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Celiac Dsease
Microbiota
Mucosal Immunity
topic Celiac Dsease
Microbiota
Mucosal Immunity
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 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.
Fil: Caminero, Alberto. Mc Master University; Canadá
Fil: McCarville, Justin L.. Mc Master University; Canadá
Fil: Galipeau, Heather J.. Mc Master University; Canadá
Fil: Deraison, Celine. Université de Toulouse; Francia
Fil: Bernier, Steve P.. Mc Master University; Canadá
Fil: Constante, Marco. Mc Master University; Canadá
Fil: Rolland, Corinne. Université de Toulouse; Francia
Fil: Meisel, Marlies. University of Chicago; Estados Unidos
Fil: Murray, Joseph A.. Mayo Clinic College of Medicine; Estados Unidos
Fil: Yu, Xuechen B.. Columbia University; Estados Unidos
Fil: Alaedini, Armin. Columbia University; Estados Unidos
Fil: Coombes, Brian K.. Mc Master University; Canadá
Fil: Bercik, Premysl. Mc Master University; Canadá
Fil: Southward, Carolyn M.. Mc Master University; Canadá
Fil: Ruf, Wolfram. The Scripps Research Institute; Estados Unidos. Johannes Gutenberg Universitat Mainz; Alemania
Fil: Jabri, Bana. University of Chicago; Estados Unidos
Fil: Chirdo, Fernando Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina
Fil: Casqueiro, Javier. Universidad de León; España
Fil: Surette, Michael G.. Mc Master University; Canadá
Fil: Vergnolle, Nathalie. Université de Toulouse; Francia
Fil: Verdu, Elena F.. Mc Master University; Canadá
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.
publishDate 2019
dc.date.none.fl_str_mv 2019-03-13
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/152154
Caminero, Alberto; McCarville, Justin L.; Galipeau, Heather J.; Deraison, Celine; Bernier, Steve P.; et al.; Duodenal bacterial proteolytic activity determines sensitivity to dietary antigen through protease-activated receptor-2; Nature Publishing Group; Nature Communications; 10; 1; 13-3-2019; 1-14
2041-1723
CONICET Digital
CONICET
url http://hdl.handle.net/11336/152154
identifier_str_mv Caminero, Alberto; McCarville, Justin L.; Galipeau, Heather J.; Deraison, Celine; Bernier, Steve P.; et al.; Duodenal bacterial proteolytic activity determines sensitivity to dietary antigen through protease-activated receptor-2; Nature Publishing Group; Nature Communications; 10; 1; 13-3-2019; 1-14
2041-1723
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1038/s41467-019-09037-9
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41467-019-09037-9
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.993085

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