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Immunity. 2018 Sep 18;49(3):560-575.e6. doi: 10.1016/j.immuni.2018.07.016. Epub 2018 Aug 28.

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

Author information

1
Division of Immunology & Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
2
Division of Immunology & Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. Electronic address: barton@berkeley.edu.

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.

KEYWORDS:

Paneth cells; TLR; innate immunity; intestinal epithelial cells; intestinal homeostasis

PMID:
30170812
PMCID:
PMC6152941
DOI:
10.1016/j.immuni.2018.07.016
[Indexed for MEDLINE]
Free PMC Article

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