title: Intraluminal administration of poly I:C causes an enteropathy that is exacerbated by administration of oral dietary antigen.
abstract: Systemic administration of polyinosinic:polycytidylic acid (poly I:C), mimics virally-induced activation of TLR3 signalling causing acute small intestine damage, but whether and how mucosal administration of poly I:C causes enteropathy is less clear. Our aim was to investigate the inflammatory pathways elicited after intraluminal administration of poly I:C and determine acute and delayed consequences of this locally induced immune activation. Intraluminal poly I:C induced rapid mucosal immune activation in C57BL/6 mice involving IFNβ and the CXCL10/CXCR3 axis, that may drive inflammation towards a Th1 profile. Intraluminal poly I:C also caused enteropathy and gut dysfunction in gliadin-sensitive NOD-DQ8 mice, and this was prolonged by concomitant oral administration of gliadin. Our results indicate that small intestine pathology can be induced in mice by intraluminal administration of poly I:C and that this is exacerbated by subsequent oral delivery of a relevant dietary antigen.
authors.affiliation: Laboratorio de Investigación en el Sistema Inmune- LISIN, Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Argentina.
authors.forename: Romina E
authors.initials: RE
authors.lastname: Araya
authors.affiliation: Division of Gastroenterology, Farncombe Family Digestive Health Institute, McMaster University, Hamilton, Canada.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jury
authors.affiliation: Laboratorio de Investigación en el Sistema Inmune- LISIN, Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Argentina.
authors.forename: Constanza
authors.initials: C
authors.lastname: Bondar
authors.affiliation: Division of Gastroenterology, Farncombe Family Digestive Health Institute, McMaster University, Hamilton, Canada.
authors.forename: Elena F
authors.initials: EF
authors.lastname: Verdu
authors.affiliation: Laboratorio de Investigación en el Sistema Inmune- LISIN, Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Argentina.
authors.forename: Fernando G
authors.initials: FG
authors.lastname: Chirdo
mesh_terms: D000284:Administration, Oral; D000818:Animals; D016207:Cytokines / Q000097:blood; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005903:Gliadin / Q000008:administration & dosage* / Q000009:adverse effects*; D018836:Inflammation Mediators / Q000378:metabolism; D000072640:Interferon-Induced Helicase, IFIH1; D007410:Intestinal Diseases / Q000097:blood / Q000139:chemically induced* / Q000473:pathology*; D007413:Intestinal Mucosa / Q000187:drug effects; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D011070:Poly I-C / Q000008:administration & dosage* / Q000009:adverse effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D012333:RNA, Messenger; D051196:Toll-Like Receptor 3; D005903:Gliadin; C503356:Ddx58 protein, mouse; C510592:Ifih1 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1; D011070:Poly I-C