P31-43, an undigested gliadin peptide, mimics and enhances the innate immune response to viruses and interferes with endocytic trafficking: a role in celiac disease

Merlin Nanayakkara; Giuliana Lania; Mariantonia Maglio; Renata Auricchio; Cristiana De Musis; Valentina Discepolo; Erasmo Miele; Bana Jabri; Riccardo Troncone; Salvatore Auricchio; Maria Vittoria Barone

doi:10.1038/s41598-018-28830-y

P31-43, an undigested gliadin peptide, mimics and enhances the innate immune response to viruses and interferes with endocytic trafficking: a role in celiac disease

Sci Rep. 2018 Jul 17;8(1):10821. doi: 10.1038/s41598-018-28830-y.

Affiliations

¹ Department of Translational Medical Science (Section of Paediatrics) and ELFID (European Laboratory for the Investigation of Food-Induced Disease), University of Naples, Federico II, Naples, 80131, Italy.
² Department of Medicine, University of Chicago, Chicago, Illinois, 60637, USA.
³ Department of Translational Medical Science (Section of Paediatrics) and ELFID (European Laboratory for the Investigation of Food-Induced Disease), University of Naples, Federico II, Naples, 80131, Italy. [email protected].

Abstract

Celiac disease (CD) is an autoimmune disease characterized by inflammation of the intestinal mucosa due to an immune response to wheat gliadins. Some gliadin peptides are resistant to intestinal digestion (e.g., A-gliadin P31-43) and induce a stress/innate immune response, but the reason why they are dangerous in the intestines of patients with CD is unknown. In the present study, P31-43 activated IFN-α, a mediator of the innate immune response in CD, in the intestine of subjects with CD and an enterocyte cell line, CaCo-2. P31-43 cooperated with a viral ligand to activate the TLR7 pathway by interfering with endocytic trafficking. Based on these results, the vesicular pathway regulates the innate/inflammatory response to viral ligands and bioactive dietary peptides. Suggesting that together with viral infections, alimentary proteins able to mimic and potentiate the innate immune response to viruses, can trigger an autoimmune disease such as CD.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Caco-2 Cells
Celiac Disease / immunology
Celiac Disease / pathology*
Child
Child, Preschool
Diet, Gluten-Free
Endocytosis / drug effects*
Enterocytes / cytology
Enterocytes / drug effects
Enterocytes / metabolism
Female
Gliadin / chemistry
Gliadin / pharmacology*
Guanosine / analogs & derivatives
Guanosine / pharmacology
Humans
Immunity, Innate / drug effects*
Interferon-alpha / metabolism
Intestinal Mucosa / metabolism
Intestinal Mucosa / pathology
Male
Myxovirus Resistance Proteins / metabolism
NF-kappa B / metabolism
Peptide Fragments / chemistry
Peptide Fragments / pharmacology*
Signal Transduction / drug effects
Toll-Like Receptor 7 / antagonists & inhibitors
Toll-Like Receptor 7 / genetics
Toll-Like Receptor 7 / metabolism

Substances

Interferon-alpha
MX1 protein, human
Myxovirus Resistance Proteins
NF-kappa B
Peptide Fragments
TLR7 protein, human
Toll-Like Receptor 7
gliadin p31-43
Guanosine
Gliadin
loxoribine