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

Author:
Vaishnava, Shipra, Behrendt, Cassie L., Ismail, Anisa S., Eckmann, Lars, Hooper, Lora V.
Source:
Proceedings of the National Academy of Sciences of the United States of America 2008 v.105 no.52 pp. 20858-20863
ISSN:
0027-8424
Subject:
Toll-like receptors, bacteria, direct contact, epithelial cells, homeostasis, intestinal microorganisms, intestinal mucosa, microbial load
Abstract:
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.
Agid:
2362729