title: Interaction of Bordetella pertussis filamentous hemagglutinin with human TLR2: identification of the TLR2-binding domain.
abstract: Filamentous hemagglutinin (FHA) is a major adhesion and virulence factor of Bordetella pertussis and also a main component of acellular pertussis vaccines. Interaction of FHA with different receptors on human epithelial and immune cells facilitates entrance and colonization of bacteria as well as immunomodulation of the host immune response. Three overlapping segments of the FHA gene were cloned in a prokaryotic expression vector and the recombinant proteins were purified. These recombinant fragments along with the native FHA protein were employed to assess their potential Toll-like receptor (TLR) stimulatory effects and to localize the TLR binding region. TLR stimulation was monitored by applying HEK293-Blue cell lines cotransfected with TLR2, 4, or 5 and a NF-κB reporter gene. Culture supernatants were checked for secretion of the reporter gene product and IL-8 as indicators of TLR stimulation. Native FHA was found to strongly stimulate TLR2, but not TLR4 or TLR5 transfected cells. Among recombinant FHA fragments only the fragment spanning amino acid residues 1544-1917 was able to exhibit the TLR2 stimulating property of FHA. Interaction of FHA with TLR2 suggests its involvement in induction of the innate immune system against Bordetella pertussis. The TLR2-binding domain of FHA may contribute to immunoprotection against pertussis infection.
authors.affiliation: Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Asgarian-Omran
authors.forename: Ali Akbar
authors.initials: AA
authors.lastname: Amirzargar
authors.forename: Sacha
authors.initials: S
authors.lastname: Zeerleder
authors.forename: Marzieh
authors.initials: M
authors.lastname: Mahdavi
authors.forename: Gerard
authors.initials: G
authors.lastname: van Mierlo
authors.forename: Shabnam
authors.initials: S
authors.lastname: Solati
authors.forename: Mahmood
authors.initials: M
authors.lastname: Jeddi-Tehrani
authors.forename: Hodjatallah
authors.initials: H
authors.lastname: Rabbani
authors.forename: Leucien
authors.initials: L
authors.lastname: Aarden
authors.forename: Fazel
authors.initials: F
authors.lastname: Shokri
mesh_terms: D018829:Adhesins, Bacterial / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology; D001422:Bacterial Adhesion / Q000235:genetics / Q000276:immunology; D001665:Binding Sites / Q000276:immunology; D001886:Bordetella pertussis / Q000276:immunology*; D002460:Cell Line; D057809:HEK293 Cells; D006801:Humans; D016328:NF-kappa B / Q000235:genetics; D010567:Pertussis Vaccine / Q000276:immunology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology; D051198:Toll-Like Receptor 5 / Q000235:genetics / Q000276:immunology; D010566:Virulence Factors, Bordetella / Q000276:immunology*; D014917:Whooping Cough / Q000276:immunology*
chemical_list: D018829:Adhesins, Bacterial; D000942:Antigens, Bacterial; D016328:NF-kappa B; D010567:Pertussis Vaccine; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C495346:TLR5 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D010566:Virulence Factors, Bordetella; C065273:filamentous hemagglutinin adhesin, Bordetella pertussis
keywords: Bordetella pertussis; TLR2; Toll-like receptor; filamentous hemagglutinin; innate immunity