Araya Romina E, Jury Jennifer, Bondar Constanza, Verdu Elena F, Chirdo Fernando G
Laboratorio de Investigación en el Sistema Inmune- LISIN, Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Argentina.
Division of Gastroenterology, Farncombe Family Digestive Health Institute, McMaster University, Hamilton, Canada.
PLoS One. 2014 Jun 10;9(6):e99236. doi: 10.1371/journal.pone.0099236. eCollection 2014.
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.
聚胞苷酸（poly I:C）可模拟病毒诱导的Toll样受体3（TLR3）信号激活，导致急性小肠损伤，但聚I:C经黏膜给药是否以及如何引起肠病尚不清楚。我们的目的是研究腔内给予聚I:C后引发的炎症途径，并确定这种局部诱导的免疫激活的急性和延迟后果。腔内聚I:C在C57BL/6小鼠中诱导快速的黏膜免疫激活，涉及干扰素β（IFNβ）和CXC趋化因子配体10（CXCL10）/CXC趋化因子受体3（CXCR3）轴，这可能会使炎症趋向于1型辅助性T细胞（Th1）特征。腔内聚I:C还在麦醇溶蛋白敏感的非肥胖糖尿病（NOD）-DQ8小鼠中引起肠病和肠道功能障碍，并且通过同时口服麦醇溶蛋白可使其延长。我们的结果表明，腔内给予聚I:C可在小鼠中诱导小肠病理变化，并且随后口服相关饮食抗原会使其加剧。
