The TLR3/TICAM-1 signal constitutively controls spontaneous polyposis through suppression of c-Myc in Apc Min/+ mice

Background: intestinal tumorigenesis is promoted by myeloid differentiation primary response gene 88 (myd88) activation in response to the components of microbiota in apc min/+ mice. microbiota also contains double-stranded rna (dsrna),a ligand for tlr3,which activates the toll-like receptor adaptor molecule 1 (ticam-1,also known as trif) pathway. methods: we established apc min/+ ticam1 -/- mice and their survival was compared to survival of apc min/+ myd88 -/- and wild-type (wt) mice. the properties of polyps were investigated using immunofluorescence staining and rt-pcr analysis. results: we demonstrate that ticam-1 is essential for suppression of polyp formation in apc min/+ mice. ticam-1 knockout resulted in shorter survival of mice compared to wt mice or mice with knockout of myd88 in the apc min/+ background. polyps were more frequently formed in the distal intestine of apc min/+ ticam1 -/- mice than in apc min/+ mice. infiltration of immune cells such as cd11b+ and cd8α+ cells into the polyps was detected histologically. cd11b and cd8α mrnas were increased in polyps of apc min/+ ticam1 -/- mice compared to apc min/+ mice. gene expression of inducible nitric oxide synthase (inos),interferon (ifn)-γ,cxcl9 and il-12p40 was increased in polyps of apc min/+ ticam1 -/- mice. mrna and protein expression of c-myc,a critical transcription factor for inflammation-associated polyposis,were increased in polyps of apc min/+ ticam1 -/- mice. a lactobacillus strain producing dsrna was detected in feces of apc min/+ mice. conclusion: these results imply that the tlr3/ticam-1 pathway inhibits polyposis through suppression of c-myc expression and supports long survival in apc min/+ mice. © 2017 the author(s).