TLR3, TRIF, and caspase 8 determine double-stranded RNA-induced epithelial cell death and survival in vivo.

ABSTRACT: TLR3 signaling is activated by dsRNA, a virus-associated molecular pattern. Injection of dsRNA into mice induced a rapid, dramatic, and reversible remodeling of the small intestinal mucosa with significant villus shortening. Villus shortening was preceded by increased caspase 3 and 8 activation and apoptosis of intestinal epithelial cells (IECs) located in the mid to upper villus with ensuing luminal fluid accumulation and diarrhea because of an increased secretory state. Mice lacking TLR3 or the adaptor molelcule TRIF mice were completely protected from dsRNA-induced IEC apoptosis, villus shortening, and diarrhea. dsRNA-induced apoptosis was independent of TNF signaling. Notably, NF-κB signaling through IκB kinase β protected crypt IECs but did not protect villus IECs from dsRNA-induced o

SUBMITTER: McAllister CS 

PROVIDER: S-EPMC3551582 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature