PLoS ONE (Jan 2014)

Intraluminal administration of poly I:C causes an enteropathy that is exacerbated by administration of oral dietary antigen.

  • Romina E Araya,
  • Jennifer Jury,
  • Constanza Bondar,
  • Elena F Verdu,
  • Fernando G Chirdo

DOI
https://doi.org/10.1371/journal.pone.0099236
Journal volume & issue
Vol. 9, no. 6
p. e99236

Abstract

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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.