Helicobacter pylori flagellin evades toll-like receptor 5-mediated innate immunity.
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.
Gewirtz
Andrew T
AT
Epithelial Pathobiology Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
Yu
Yimin
Y
Krishna
Uma S
US
Israel
Dawn A
DA
Lyons
Sean L
SL
Peek
Richard M
RM
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
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