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

Autores
Araya, Romina Elizabeth; Gomez Castro, Maria Florencia; Carasi, Paula; McCarville, Justin L.; Jury, Jennifer; Mowat, Allan M.; Verdu, Elena F.; Chirdo, Fernando Gabriel
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Araya, Romina Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina
Fil: Gomez Castro, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina
Fil: Carasi, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de la Plata. Facultad de Cs.veterinarias. Departamento de Microbiología. Cátedra de Microbiología; Argentina
Fil: McCarville, Justin L.. McMaster University; Canadá
Fil: Jury, Jennifer. McMaster University; Canadá
Fil: Mowat, Allan M.. University of Glasgow; Reino Unido
Fil: Verdu, Elena F.. McMaster University; Canadá
Fil: Chirdo, Fernando Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina
Materia
CELIAC DISEASE
INNATE IMMUNITY
P31-43
POLYINOSINIC:POLYCYTIDYLIC ACID
SMALL INTESTINE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/54535
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/54535
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Mechanisms of innate immune activation by gluten peptide p31-43 in miceAraya, Romina ElizabethGomez Castro, Maria FlorenciaCarasi, PaulaMcCarville, Justin L.Jury, JenniferMowat, Allan M.Verdu, Elena F.Chirdo, Fernando GabrielCELIAC DISEASEINNATE IMMUNITYP31-43POLYINOSINIC:POLYCYTIDYLIC ACIDSMALL INTESTINEhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Celiac 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.Fil: Araya, Romina Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Gomez Castro, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Carasi, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de la Plata. Facultad de Cs.veterinarias. Departamento de Microbiología. Cátedra de Microbiología; ArgentinaFil: McCarville, Justin L.. McMaster University; CanadáFil: Jury, Jennifer. McMaster University; CanadáFil: Mowat, Allan M.. University of Glasgow; Reino UnidoFil: Verdu, Elena F.. McMaster University; CanadáFil: Chirdo, Fernando Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaAmerican Physiological Society2016-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/54535Araya, Romina Elizabeth; Gomez Castro, Maria Florencia; Carasi, Paula; McCarville, Justin L.; Jury, Jennifer; et al.; Mechanisms of innate immune activation by gluten peptide p31-43 in mice; American Physiological Society; American Journal of Physiology-gastrointestinal and Liver Physiology; 311; 1; 7-2016; G40-G490193-1857CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1152/ajpgi.00435.2015info:eu-repo/semantics/altIdentifier/url/https://www.physiology.org/doi/10.1152/ajpgi.00435.2015info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:05:45Zoai:ri.conicet.gov.ar:11336/54535instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:05:46.196CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Mechanisms of innate immune activation by gluten peptide p31-43 in mice
title Mechanisms of innate immune activation by gluten peptide p31-43 in mice
spellingShingle Mechanisms of innate immune activation by gluten peptide p31-43 in mice
Araya, Romina Elizabeth
CELIAC DISEASE
INNATE IMMUNITY
P31-43
POLYINOSINIC:POLYCYTIDYLIC ACID
SMALL INTESTINE
title_short Mechanisms of innate immune activation by gluten peptide p31-43 in mice
title_full Mechanisms of innate immune activation by gluten peptide p31-43 in mice
title_fullStr Mechanisms of innate immune activation by gluten peptide p31-43 in mice
title_full_unstemmed Mechanisms of innate immune activation by gluten peptide p31-43 in mice
title_sort Mechanisms of innate immune activation by gluten peptide p31-43 in mice
dc.creator.none.fl_str_mv Araya, Romina Elizabeth
Gomez Castro, Maria Florencia
Carasi, Paula
McCarville, Justin L.
Jury, Jennifer
Mowat, Allan M.
Verdu, Elena F.
Chirdo, Fernando Gabriel
author Araya, Romina Elizabeth
author_facet Araya, Romina Elizabeth
Gomez Castro, Maria Florencia
Carasi, Paula
McCarville, Justin L.
Jury, Jennifer
Mowat, Allan M.
Verdu, Elena F.
Chirdo, Fernando Gabriel
author_role author
author2 Gomez Castro, Maria Florencia
Carasi, Paula
McCarville, Justin L.
Jury, Jennifer
Mowat, Allan M.
Verdu, Elena F.
Chirdo, Fernando Gabriel
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CELIAC DISEASE
INNATE IMMUNITY
P31-43
POLYINOSINIC:POLYCYTIDYLIC ACID
SMALL INTESTINE
topic CELIAC DISEASE
INNATE IMMUNITY
P31-43
POLYINOSINIC:POLYCYTIDYLIC ACID
SMALL INTESTINE
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 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.
Fil: Araya, Romina Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina
Fil: Gomez Castro, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina
Fil: Carasi, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de la Plata. Facultad de Cs.veterinarias. Departamento de Microbiología. Cátedra de Microbiología; Argentina
Fil: McCarville, Justin L.. McMaster University; Canadá
Fil: Jury, Jennifer. McMaster University; Canadá
Fil: Mowat, Allan M.. University of Glasgow; Reino Unido
Fil: Verdu, Elena F.. McMaster University; Canadá
Fil: Chirdo, Fernando Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina
description 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.
publishDate 2016
dc.date.none.fl_str_mv 2016-07
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/54535
Araya, Romina Elizabeth; Gomez Castro, Maria Florencia; Carasi, Paula; McCarville, Justin L.; Jury, Jennifer; et al.; Mechanisms of innate immune activation by gluten peptide p31-43 in mice; American Physiological Society; American Journal of Physiology-gastrointestinal and Liver Physiology; 311; 1; 7-2016; G40-G49
0193-1857
CONICET Digital
CONICET
url http://hdl.handle.net/11336/54535
identifier_str_mv Araya, Romina Elizabeth; Gomez Castro, Maria Florencia; Carasi, Paula; McCarville, Justin L.; Jury, Jennifer; et al.; Mechanisms of innate immune activation by gluten peptide p31-43 in mice; American Physiological Society; American Journal of Physiology-gastrointestinal and Liver Physiology; 311; 1; 7-2016; G40-G49
0193-1857
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1152/ajpgi.00435.2015
info:eu-repo/semantics/altIdentifier/url/https://www.physiology.org/doi/10.1152/ajpgi.00435.2015
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Physiological Society
publisher.none.fl_str_mv American Physiological Society
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.982451

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