A Map of Toll-like Receptor Expression in the Intestinal Epithelium Reveals Distinct Spatial, Cell Type-Specific, and Temporal Patterns

Signaling by Toll-like receptors (TLRs) on intestinal epithelial cells (IECs) is critical for intestinal homeostasis. To visualize epithelial expression of individual TLRs in vivo, we generated five strains of reporter mice. These mice revealed that TLR expression varied dramatically along the length of the intestine. Indeed, small intestine (SI) IECs expressed low levels of multiple TLRs that were highly expressed by colonic IECs. TLR5 expression was restricted to Paneth cells in the SI epithelium. Intestinal organoid experiments revealed that TLR signaling in Paneth cells or colonic IECs induced a core set of host defense genes, but this set did not include antimicrobial peptides, which instead were induced indirectly by inflammatory cytokines. This comprehensive blueprint of TLR expression and function in IECs reveals unexpected diversity in the responsiveness of IECs to microbial stimuli, and together with the associated reporter strains, provides a resource for further study of innate immunity. [Display omitted] •Reporter mice reveal distinct patterns of TLR expression in SI and colon IECs•TLR5 expression is restricted to Paneth cells in the SI epithelium•TLR signaling in IECs induces a specific program of host defense genes•IEC antimicrobial peptides are not induced by TLRs, but rather by immune signals Price et al. generate five strains of reporter mice to visualize the expression of individual TLRs on intestinal epithelial cells (IECs). Their findings reveal unexpected diversity in the temporal and spatial patterns of TLR expression and in the responsiveness of IECs to microbial stimuli.