title: Helicobacter pylori flagellin evades toll-like receptor 5-mediated innate immunity.
abstract: Helicobacter pylori colonizes the human stomach for decades unless pharmacologically eradicated. We hypothesized that this flagellated pathogen escapes immune clearance, in part, by avoiding detection by the flagellin receptor Toll-like receptor 5 (TLR5). In contrast to other gram-negative microbes, H. pylori did not release flagellin. Furthermore, recombinant H. pylori flagellin (FlaA) was significantly less potent (1000-fold) than Salmonella typhimurium flagellin in activating TLR5-mediated interleukin (IL)-8 secretion. TLR5 can mediate flagellin-induced IL-8 secretion via p38 mitogen-activated protein kinase signaling; however, compared with potent induction by S. typhimurium flagellin, H. pylori FlaA-dependent p38 activation was substantially attenuated. In addition, disruption of H. pylori flaA decreased motility but had no effect on H. pylori-induced IL-8 secretion, which indicates that H. pylori flagellin plays no role in activating epithelial orchestration of inflammation. We conclude that H. pylori evades TLR5-mediated detection, which may contribute to its long-term persistence in individual hosts.
authors.affiliation: Epithelial Pathobiology Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Gewirtz
authors.forename: Yimin
authors.initials: Y
authors.lastname: Yu
authors.forename: Uma S
authors.initials: US
authors.lastname: Krishna
authors.forename: Dawn A
authors.initials: DA
authors.lastname: Israel
authors.forename: Sean L
authors.initials: SL
authors.lastname: Lyons
authors.forename: Richard M
authors.initials: RM
authors.lastname: Peek
mesh_terms: D000818:Animals; D015153:Blotting, Western; D017077:Culture Media, Conditioned; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells; D005408:Flagellin / Q000235:genetics / Q000276:immunology*; D005753:Gastric Mucosa / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D016481:Helicobacter Infections / Q000276:immunology*; D016480:Helicobacter pylori / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016209:Interleukin-8 / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology*; D016254:Mutagenesis, Insertional; D011956:Receptors, Cell Surface / Q000276:immunology*; D011994:Recombinant Proteins; D012486:Salmonella typhimurium / Q000276:immunology; D013272:Stomach Diseases / Q000276:immunology* / Q000382:microbiology; D051198:Toll-Like Receptor 5; D051193:Toll-Like Receptors
chemical_list: D017077:Culture Media, Conditioned; D016209:Interleukin-8; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C495346:TLR5 protein, human; D051198:Toll-Like Receptor 5; D051193:Toll-Like Receptors; D005408:Flagellin