title: Helicobacter pylori flagellins have very low intrinsic activity to stimulate human gastric epithelial cells via TLR5.
abstract: Helicobacter pylori is a flagellated chronic pathogen, which colonizes the gastric mucus and mucosal cell surfaces. Flagella and motility are essential for the survival of this bacterium in the stomach environment. Flagellins of several bacterial species are potent activators of the human innate immune system by binding to TOLL-like receptor 5 (TLR5). The possible role of the two H. pylori flagellins FlaA and FlaB in stimulation of the innate immune system and induction of IL-8 release by human gastric epithelial cells was investigated in this study. Transcription and expression of TLR5 in three different human gastric epithelial cell lines was demonstrated. Salmonella enterica serovar Typhimurium FliC flagellin was able to activate human gastric epithelial cells. TLR5 transcription was modulated by H. pylori infection. However, both H. pylori flagellins appeared to possess no immunostimulatory potential on human gastric cells via TLR5, despite their extensive amino acid homology to stimulating flagellins of other bacterial species. The evolutionary development of such unique flagellins of low activating potential is proposed to be a novel mechanism of H. pylori to preserve the essential function of its flagella during chronic colonization of the stomach and to evade the deleterious host immune responses.
authors.affiliation: Institute for Hygiene and Microbiology, University of Wuerzburg, Josef-Schneider-Strasse 2, 97080 Wuerzburg, Germany.
authors.forename: Sae Kyung
authors.initials: SK
authors.lastname: Lee
authors.forename: Allison
authors.initials: A
authors.lastname: Stack
authors.forename: Elena
authors.initials: E
authors.lastname: Katzowitsch
authors.forename: Shin Ichi
authors.initials: SI
authors.lastname: Aizawa
authors.forename: Sebastian
authors.initials: S
authors.lastname: Suerbaum
authors.forename: Christine
authors.initials: C
authors.lastname: Josenhans
mesh_terms: D002460:Cell Line; D005407:Flagella / Q000502:physiology / Q000648:ultrastructure*; D005408:Flagellin / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000502:physiology; D016480:Helicobacter pylori / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D008562:Membrane Glycoproteins; D011485:Protein Binding; D011956:Receptors, Cell Surface; D015398:Signal Transduction / Q000187:drug effects; D051198:Toll-Like Receptor 5; D051193:Toll-Like Receptors
chemical_list: D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495346:TLR5 protein, human; D051198:Toll-Like Receptor 5; D051193:Toll-Like Receptors; D005408:Flagellin