Mechanisms of innate immune activation by gluten peptide p31-43 in mice

Araya, R. E., Gomez Castro, M. F., Carasi, P., McCarville, J. L., Jury, J., Mowat, A. M., Verdu, E. F. and Chirdo, F. G. (2016) Mechanisms of innate immune activation by gluten peptide p31-43 in mice. American Journal of Physiology: Gastrointestinal and Liver Physiology, 311(1), G40-G49. (doi:10.1152/ajpgi.00435.2015) (PMID:27151946)

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Abstract

Celiac disease (CD) is an immune-mediated enteropathy triggered by gluten in genetically susceptible individuals. Innate immunity contributes to the pathogenesis of CD, but the mechanisms remain poorly understood. Although previous in vitro work suggests that gliadin peptide p31-43 acts as an innate immune trigger, the underlying pathways are unclear and have not been explored in vivo. Here we show that intraluminal delivery of p31-43 induces morphological changes in the small intestinal mucosa of normal mice consistent with those seen in CD, including increased cell death and expression of inflammatory mediators. The effects of p31-43 were dependent on MyD88 and type I IFNs, but not Toll-like receptor 4 (TLR4), and were enhanced by coadministration of the TLR3 agonist polyinosinic:polycytidylic acid. Together, these results indicate that gliadin peptide p31-43 activates the innate immune pathways in vivo, such as IFN-dependent inflammation, relevant to CD. Our findings also suggest a common mechanism for the potential interaction between dietary gluten and viral infections in the pathogenesis of CD.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mowat, Professor Allan
Authors: Araya, R. E., Gomez Castro, M. F., Carasi, P., McCarville, J. L., Jury, J., Mowat, A. M., Verdu, E. F., and Chirdo, F. G.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:American Journal of Physiology: Gastrointestinal and Liver Physiology
Publisher:American Physiological Society
ISSN:0193-1857
ISSN (Online):1522-1547
Published Online:05 May 2016
Copyright Holders:Copyright © 2016 American Physiological Society
First Published:First published in American Journal of Physiology: Gastrointestinal and Liver Physiology 311(1): G40-49
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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