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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Alberto Caminero, Justin L. McCarville, Heather J. Galipeau, Celine Deraison, Steve P. Bernier, Marco Constante, Corinne Rolland, Marlies Meisel, Joseph A. Murray, Xuechen B. Yu, Armin Alaedini, Brian K. Coombes, Premysl Bercik, Carolyn M. Southward, Wolfram Ruf, Bana Jabri, Fernando G. Chirdo, Javier Casqueiro, Michael G. Surette, Nathalie Vergnolle, Elena F. Verdu

ABSTRACT

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. More... »

PAGES

1198

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-019-09037-9

    DOI

    http://dx.doi.org/10.1038/s41467-019-09037-9

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1112734574

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30867416


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