title: Paneth cells directly sense gut commensals and maintain homeostasis at the intestinal host-microbial interface.
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.
authors.affiliation: The Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Shipra
authors.initials: S
authors.lastname: Vaishnava
authors.forename: Cassie L
authors.initials: CL
authors.lastname: Behrendt
authors.forename: Anisa S
authors.initials: AS
authors.lastname: Ismail
authors.forename: Lars
authors.initials: L
authors.lastname: Eckmann
authors.forename: Lora V
authors.initials: LV
authors.lastname: Hooper
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000276:immunology; D001419:Bacteria / Q000276:immunology*; D018988:Bacterial Translocation / Q000276:immunology*; D006706:Homeostasis / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology*; D019879:Paneth Cells / Q000276:immunology* / Q000382:microbiology; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology*
chemical_list: D000890:Anti-Infective Agents; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D051193:Toll-Like Receptors