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

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 VergnolleElena F. Verdu

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish (US)
Article number1198
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

Fingerprint

PAR-2 Receptor
protease
Glutens
antigens
Celiac Disease
food
Antigens
pseudomonas
sensitivity
Food
mice
Proteobacteria
pathogens
Biopsy
Pancreatic Elastase
Pathogens
microorganisms
Pseudomonas
Inbred C57BL Mouse
genes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Caminero, A., McCarville, J. L., Galipeau, H. J., Deraison, C., Bernier, S. P., Constante, M., ... Verdu, E. F. (2019). Duodenal bacterial proteolytic activity determines sensitivity to dietary antigen through protease-activated receptor-2. Nature communications, 10(1), [1198]. https://doi.org/10.1038/s41467-019-09037-9

Duodenal bacterial proteolytic activity determines sensitivity to dietary antigen through protease-activated receptor-2. / 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 G.; Casqueiro, Javier; Surette, Michael G.; Vergnolle, Nathalie; Verdu, Elena F.

In: Nature communications, Vol. 10, No. 1, 1198, 01.12.2019.

Research output: Contribution to journalArticle

Caminero, A, McCarville, JL, Galipeau, HJ, Deraison, C, Bernier, SP, Constante, M, Rolland, C, Meisel, M, Murray, JA, Yu, XB, Alaedini, A, Coombes, BK, Bercik, P, Southward, CM, Ruf, W, Jabri, B, Chirdo, FG, Casqueiro, J, Surette, MG, Vergnolle, N & Verdu, EF 2019, 'Duodenal bacterial proteolytic activity determines sensitivity to dietary antigen through protease-activated receptor-2', Nature communications, vol. 10, no. 1, 1198. https://doi.org/10.1038/s41467-019-09037-9
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 G. ; Casqueiro, Javier ; Surette, Michael G. ; Vergnolle, Nathalie ; Verdu, Elena F. / Duodenal bacterial proteolytic activity determines sensitivity to dietary antigen through protease-activated receptor-2. In: Nature communications. 2019 ; Vol. 10, No. 1.
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