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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Oral
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Animals
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Cytokines / blood
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DEAD Box Protein 58
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DEAD-box RNA Helicases / genetics
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DEAD-box RNA Helicases / metabolism
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Disease Progression*
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Female
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Gene Expression Regulation / drug effects
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Gliadin / administration & dosage*
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Gliadin / adverse effects*
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Inflammation Mediators / metabolism
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Interferon-Induced Helicase, IFIH1
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Intestinal Diseases / blood
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Intestinal Diseases / chemically induced*
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Intestinal Diseases / pathology*
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Intestinal Mucosa / drug effects
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Intestine, Small / drug effects
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Intestine, Small / metabolism
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Mice, Inbred C57BL
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Mice, Inbred NOD
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Poly I-C / administration & dosage*
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Poly I-C / adverse effects*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Real-Time Polymerase Chain Reaction
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Toll-Like Receptor 3 / genetics
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Toll-Like Receptor 3 / metabolism
Substances
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Cytokines
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Inflammation Mediators
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RNA, Messenger
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Toll-Like Receptor 3
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Gliadin
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Ddx58 protein, mouse
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Ifih1 protein, mouse
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DEAD Box Protein 58
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DEAD-box RNA Helicases
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Interferon-Induced Helicase, IFIH1
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Poly I-C