title: Activation of human dendritic cells by the PorA protein of Neisseria meningitidis.
abstract: The major porin proteins present in the outer membrane of Neisseria meningitidis, the causative agent of life-threatening meningitis and septicaemia, are believed to have potent immunostimulatory effects. In this study, the interactions between human monocyte-derived dendritic cells (mo-DC) and the PorA porin were investigated, in order to reveal the role of this protein in promoting innate and adaptive immune responses. Recombinant (r)PorA induced mo-DC maturation, as reflected by reduced receptor-mediated endocytosis, increased production of the chemokines IL-8, RANTES, MIP-1 alpha and MIP-1 beta and augmented expression of the surface markers CD40, CD54, CD80, CD86 and major histocompatibility complex class II molecules. However, rPorA induced either low level or no significant secretion of pro-inflammatory cytokines from mo-DC. The protein potently augmented the capacity of mo-DC to activate both allogeneic CD4(+) memory T-cells and CD4(+)RA(+) naïve T-cells. In addition, rPorA appeared to inhibit the production of IL-12p70 that follows from the interaction between CD40 on the mo-DC and CD40-ligand on T-cells, thereby directing T-cell differentiation towards a Th2 type response. These data demonstrate that PorA is involved in DC activation and in influencing the nature of the T-helper immune response, which are important properties for generating antibody responses required for protective immunity against meningococci and for determining the immuno-adjuvant effects of this protein.
authors.affiliation: Dermatopharmacology Unit, Division of Infection, Inflammation and Repair, Southampton General Hospital, Southampton SO16 6YD, UK.
authors.forename: Tamara
authors.initials: T
authors.lastname: Al-Bader
authors.forename: Keith A
authors.initials: KA
authors.lastname: Jolley
authors.forename: Holly E
authors.initials: HE
authors.lastname: Humphries
authors.forename: Judith
authors.initials: J
authors.lastname: Holloway
authors.forename: John E
authors.initials: JE
authors.lastname: Heckels
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Semper
authors.forename: Peter S
authors.initials: PS
authors.lastname: Friedmann
authors.forename: Myron
authors.initials: M
authors.lastname: Christodoulides
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D004705:Endocytosis; D006801:Humans; D008213:Lymphocyte Activation; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D009345:Neisseria meningitidis / Q000276:immunology* / Q000378:metabolism; D018272:Porins / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D015703:Antigens, CD; D018925:Chemokines; D016207:Cytokines; D018272:Porins; D011994:Recombinant Proteins; C057699:porin protein, Neisseria