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Interaction of Bordetella pertussis filamentous hemagglutinin with human TLR2: identification of the TLR2‐binding domain |
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| Authors: | Hossein Asgarian‐Omran Ali Akbar Amirzargar Sacha Zeerleder Marzieh Mahdavi Gerard van Mierlo Shabnam Solati Mahmood Jeddi‐Tehrani Hodjatallah Rabbani Leucien Aarden Fazel Shokri |
| Affiliation: | 1. Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran;2. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran;3. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran;4. Department of Immunopathology, Sanquin Research Institute, Amsterdam, The Netherlands;5. Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands;6. Avicenna Research Institute, Monoclonal Antibody Research Center, ACECR, Tehran, Iran |
| 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. |
| Keywords: | Bordetella pertussis filamentous hemagglutinin innate immunity Toll‐like receptor TLR2 |