title: Bordetella pertussis filamentous hemagglutinin itself does not trigger anti-inflammatory interleukin-10 production by human dendritic cells.
abstract: Filamentous hemagglutinin (FHA) is an important adhesin of the whooping cough agent Bordetella pertussis and is contained in most acellular pertussis vaccines. Recently, FHA was proposed to exert an immunomodulatory activity through induction of tolerogenic IL-10 secretion from dendritic cells. We have re-evaluated the cytokine-inducing activity of FHA, placing specific emphasis on the role of the residual endotoxin contamination of FHA preparations. We show that endotoxin depletion did not affect the capacity of FHA to bind primary human monocyte-derived dendritic cells, while it abrogated the capacity of FHA to elicit TNF-α and IL-10 secretion and strongly reduced its capacity to trigger IL-6 production. The levels of cytokines induced by the different FHA preparations correlated with their residual contents of B. pertussis endotoxin. Moreover, FHA failed to trigger cytokine secretion in the presence of antibodies that block TLR2 and/or TLR4 signaling. The TLR2 signaling capacity appeared to be linked to the presence of endotoxin-associated components in FHA preparations and not to the FHA protein itself. These results show that the endotoxin-depleted FHA protein does not induce cytokine release from human dendritic cells.
authors.affiliation: Institute of Microbiology of the Czech Academy of Sciences, v.v.i., Videnska 1083, 142 20 Prague, Czech Republic.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Villarino Romero
authors.affiliation: Institute of Microbiology of the Czech Academy of Sciences, v.v.i., Videnska 1083, 142 20 Prague, Czech Republic.
authors.forename: Shakir
authors.initials: S
authors.lastname: Hasan
authors.affiliation: Bacterial Vaccine Discovery & Early Development, Janssen, Archimedesweg 4-6, 2333 CN Leiden, The Netherlands.
authors.forename: Kellen
authors.initials: K
authors.lastname: Faé
authors.affiliation: Institute of Microbiology of the Czech Academy of Sciences, v.v.i., Videnska 1083, 142 20 Prague, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Holubova
authors.affiliation: Bacterial Vaccine Discovery & Early Development, Janssen, Archimedesweg 4-6, 2333 CN Leiden, The Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Geurtsen
authors.affiliation: Institute of Microbiology of the Czech Academy of Sciences, v.v.i., Videnska 1083, 142 20 Prague, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Schwarzer
authors.affiliation: Institute of Microbiology of the Czech Academy of Sciences, v.v.i., Videnska 1083, 142 20 Prague, Czech Republic.
authors.forename: Selma
authors.initials: S
authors.lastname: Wiertsema
authors.affiliation: Institute of Microbiology of the Czech Academy of Sciences, v.v.i., Videnska 1083, 142 20 Prague, Czech Republic.
authors.forename: Radim
authors.initials: R
authors.lastname: Osicka
authors.affiliation: Bacterial Vaccine Discovery & Early Development, Janssen, Archimedesweg 4-6, 2333 CN Leiden, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Poolman
authors.affiliation: Institute of Microbiology of the Czech Academy of Sciences, v.v.i., Videnska 1083, 142 20 Prague, Czech Republic. Electronic address: sebo@biomed.cas.cz.
authors.forename: Peter
authors.initials: P
authors.lastname: Sebo
mesh_terms: D018829:Adhesins, Bacterial / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000276:immunology*
chemical_list: D018829:Adhesins, Bacterial; D010566:Virulence Factors, Bordetella; C065273:filamentous hemagglutinin adhesin, Bordetella pertussis; D016753:Interleukin-10
keywords: Bordetella pertussis; Cytokine; Dendritic cell; Endotoxin; Filamentous hemagglutinin; Toll-like receptor.