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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Detalles Bibliográficos
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:
Biología
Proteases
Microbe-host interactions
Food sensitivities
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/107005
http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC6416356&blobtype=pdf
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
Descripción
Sumario: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.

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