title: Human dendritic cell maturation and cytokine secretion upon stimulation with Bordetella pertussis filamentous haemagglutinin.
abstract: In addition to antibodies, Th1-type T cell responses are also important for long-lasting protection against pertussis. However, upon immunization with the current acellular vaccines, many children fail to induce Th1-type responses, potentially due to immunomodulatory effects of some vaccine antigens, such as filamentous haemagglutinin (FHA). We therefore analysed the ability of FHA to modulate immune functions of human monocyte-derived dendritic cells (MDDC). FHA was purified from pertussis toxin (PTX)-deficient or from PTX- and adenylate cyclase-deficient Bordetella pertussis strains, and residual endotoxin was neutralized with polymyxin B. FHA from both strains induced phenotypic maturation of human MDDC and cytokine secretion (IL-10, IL-12p40, IL-12p70, IL-23 and IL-6). To identify the FHA domains responsible for MDDC immunomodulation, MDDC were stimulated with FHA containing a Gly→Ala substitution at its RGD site (FHA-RAD) or with an 80-kDa N-terminal moiety of FHA (Fha44), containing its heparin-binding site. Whereas FHA-RAD induced maturation and cytokine production comparable to those of FHA, Fha44 did not induce IL-10 production, but maturated MDDC at least partially. Nevertheless, Fha44 induced the secretion of IL-12p40, IL-12p70, IL-23 and IL-6 by MDDC, albeit at lower levels than FHA. Thus, FHA can modulate MDDC responses in multiple ways, and IL-10 induction can be dissociated from the induction of other cytokines.
authors.affiliation: INSERM U 1019, Lille, France; CNRS, UMR8204, Lille, France; Univ Lille Nord de France, Lille, France; Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France.
authors.forename: Violette
authors.initials: V
authors.lastname: Dirix
authors.affiliation: INSERM U 1019, Lille, France; CNRS, UMR8204, Lille, France; Univ Lille Nord de France, Lille, France; Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Mielcarek
authors.affiliation: INSERM U 1019, Lille, France; CNRS, UMR8204, Lille, France; Univ Lille Nord de France, Lille, France; Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Debrie
authors.affiliation: INSERM U 1019, Lille, France; CNRS, UMR8204, Lille, France; Univ Lille Nord de France, Lille, France; Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France.
authors.forename: Eve
authors.initials: E
authors.lastname: Willery
authors.affiliation: INSERM U 1019, Lille, France; CNRS, UMR8204, Lille, France; Univ Lille Nord de France, Lille, France; Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Alonso
authors.affiliation: Laboratory of Vaccinology and Mucosal Immunity, Université Libre de Bruxelles (U.L.B.), 808 route de Lennik, 1070 Brussels, Belgium.
authors.forename: Virginie
authors.initials: V
authors.lastname: Versheure
authors.affiliation: Laboratory of Vaccinology and Mucosal Immunity, Université Libre de Bruxelles (U.L.B.), 808 route de Lennik, 1070 Brussels, Belgium; Immunobiology Clinic, Hôpital Erasme, Université Libre de Bruxelles (U.L.B.), 808 route de Lennik, 1070 Brussels, Belgium.
authors.forename: Françoise
authors.initials: F
authors.lastname: Mascart
authors.affiliation: INSERM U 1019, Lille, France; CNRS, UMR8204, Lille, France; Univ Lille Nord de France, Lille, France; Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France. Electronic address: camille.locht@pasteur-lille.fr.
authors.forename: Camille
authors.initials: C
authors.lastname: Locht
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D001886:Bordetella pertussis / Q000276:immunology* / Q000472:pathogenicity; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D010641:Phenotype; D010566:Virulence Factors, Bordetella / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*
chemical_list: D018829:Adhesins, Bacterial; D016207:Cytokines; D010566:Virulence Factors, Bordetella; C065273:filamentous hemagglutinin adhesin, Bordetella pertussis
keywords: Bordetella; Filamentous haemagglutinin; Human dendritic cells