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

Abstract

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.

‘Layered immunity’ and the ‘neonatal window of opportunity’ – timed succession of non‐redundant phases to establish mucosal host–microbial homeostasis after birth

“…Consistent with these results, epithelial innate immune stimulation was shown to reinforce the epithelial barrier and contribute to host–microbial homeostasis . TLR5 expression in absorptive enterocytes is restricted to the pre‐weaning period . Neonatal epithelial TLR5 exerts a significant influence on the composition of the neonatal microbiota .…”

“…To investigate the establishment of mucosal host–microbial homeostasis during the early postnatal period and the pathogenesis of NEC, the ability of the intestinal epithelium to recognize microbial stimuli has been studied in much detail. Intestinal epithelial cells express innate immune receptor molecules of the toll‐like receptor, Rig I‐like receptor, nucleotide‐binding oligomerization domain (NOD) ‐like receptor and inflammasome families . Consistent with these results, epithelial innate immune stimulation was shown to reinforce the epithelial barrier and contribute to host–microbial homeostasis .…”

Lactobacillus Protects Against S. Typhimurium–Induced Intestinal Inflammation by Determining the Fate of Epithelial Proliferation and Differentiation

“…Interactions between commensal bacteria and the intestinal epithelium influence the epithelial response to injury through TLR signaling . Among intestinal epithelial cells, enteroendocrine cells express TLR1, TLR2, and TLR4, Paneth cells in the small intestinal epithelium express TLR5 . M cells express high level of TLR4 on the apical surface .…”

Post‐natal co‐development of the microbiota and gut barrier function follows different paths in the small and large intestine in piglets

“…respectively, 6,26 suggesting that adult intestinal epithelial stem cells are programmed to engage toward small intestine or colon-type epithelia. Intestinal organoids derived from small intestine or colon of adult mice recapitulate markers of small intestine and colon epithelia, F I G U R E 8 Correlation matrix of microbiota (at the family level) and mucosal parameters in the jejunum.…”