title: Cutting edge: FimH adhesin of type 1 fimbriae is a novel TLR4 ligand.
abstract: Several TLR ligands of bacterial origin induce innate immune responses. Although FimH, the adhesin portion of type 1 fimbria, plays an important role in the pathogenicity of some gram-negative bacteria, its ability to stimulate the innate immune system via TLR signaling remains unclear. In this study we report that FimH induces potent innate responses in a MyD88-dependent fashion. The FimH-induced innate activity was restricted to cells expressing TLR4. In addition, FimH was able to bind directly to TLR4. More importantly, cells unresponsive to LPS were responsive to FimH and the presence or absence of MD-2 and CD14 had no effect on FimH activity. Our data suggest that TLR4 is a functional receptor for the adhesin portion of bacterial type 1 fimbria.
authors.affiliation: Centre for Gene Therapeutics, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Mossman
authors.forename: M Firoz
authors.initials: MF
authors.lastname: Mian
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Lauzon
authors.forename: Carlton L
authors.initials: CL
authors.lastname: Gyles
authors.forename: Brian
authors.initials: B
authors.lastname: Lichty
authors.forename: Randy
authors.initials: R
authors.lastname: Mackenzie
authors.forename: Navkiran
authors.initials: N
authors.lastname: Gill
authors.forename: Ali A
authors.initials: AA
authors.lastname: Ashkar
mesh_terms: D018830:Adhesins, Escherichia coli / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D036781:Fimbriae Proteins / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008070:Lipopolysaccharides / Q000276:immunology; D008262:Macrophage Activation / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051197:Toll-Like Receptor 4 / Q000276:immunology* / Q000378:metabolism
chemical_list: D018830:Adhesins, Escherichia coli; D008024:Ligands; D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88; D051197:Toll-Like Receptor 4; C058769:fimH protein, E coli; D036781:Fimbriae Proteins