Paneth cells directly sense gut commensals and maintain homeostasis at the intestinal host-microbial interface

The intestinal epithelium is in direct contact with a vast microbiota, yet little is known about how epithelial cells defend the host against the heavy bacterial load. To address this question we studied Paneth cells, a key small intestinal epithelial lineage. We found that Paneth cells directly sen...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2008-12, Vol.105 (52), p.20858-20863
Main Authors: Vaishnava, Shipra, Behrendt, Cassie L, Ismail, Anisa S, Eckmann, Lars, Hooper, Lora V
Format: Article
Language:English
Subjects:
Animals
Anti-Infective Agents - immunology
Antimicrobials
Bacteria
Bacteria - immunology
Bacterial Translocation - immunology
Biological Sciences
Cell lines
Cells
Commensals
Enterobacteriaceae
Epithelial cells
Homeostasis
Homeostasis - immunology
Host-Pathogen Interactions - immunology
Mice
Mice, Knockout
Microbiota
Myeloid Differentiation Factor 88 - genetics
Myeloid Differentiation Factor 88 - immunology
Paneth Cells - immunology
Paneth Cells - microbiology
Salmonella
Small intestine
Studies
Toll-Like Receptors - genetics
Toll-Like Receptors - immunology
Transgenic animals
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Summary:The intestinal epithelium is in direct contact with a vast microbiota, yet little is known about how epithelial cells defend the host against the heavy bacterial load. To address this question we studied Paneth cells, a key small intestinal epithelial lineage. We found that Paneth cells directly sense enteric bacteria through cell-autonomous MyD88-dependent toll-like receptor (TLR) activation, triggering expression of multiple antimicrobial factors. Paneth cells were essential for controlling intestinal barrier penetration by commensal and pathogenic bacteria. Furthermore, Paneth cell-intrinsic MyD88 signaling limited bacterial penetration of host tissues, revealing a role for epithelial MyD88 in maintaining intestinal homeostasis. Our findings establish that gut epithelia actively sense enteric bacteria and play an essential role in maintaining host-microbial homeostasis at the mucosal interface.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0808723105