title: Recognition via the class A scavenger receptor modulates cytokine secretion by human dendritic cells after contact with Neisseria meningitidis.
abstract: Proinflammatory cytokines play a major role in the pathogenesis of meningococcal disease and their serum levels in patients are correlated with the outcome of infection. Dendritic cells initiate immunity against Neisseria meningitidis and are a major source of proinflammatory cytokines. Here we show that physical interaction of human DC with N. meningitidis via the class A scavenger receptor (SRA) modulates cytokine release by DC. Phagocytosis and uptake via SRA were shown to increase release of TNF-alpha, IL-1 beta and IL-6. In contrast, secretion of IL-8 is enhanced after recognition of N. meningitidis via SRA and not dependent on phagocytosis. Binding of N. meningitidis results in dephosphorylation of SRA but not in upregulation of SRA transcription. Unlike previously thought, not all meningococcal strains are recognized via SRA. A constitutively unencapsulated carriage isolate could be shown not to bind to SRA and induce proinflammatory cytokines independent of this receptor. In conclusion, recognition via SRA by dendritic cells is likely to play a central role in the immune response to N. meningitidis.
authors.affiliation: Institute of Hygiene and Microbiology, University of Wuerzburg, Josef-Schneider-Str. 2/E1, 97080 Wuerzburg, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Villwock
authors.forename: Corinna
authors.initials: C
authors.lastname: Schmitt
authors.forename: Stephanie
authors.initials: S
authors.lastname: Schielke
authors.forename: Matthias
authors.initials: M
authors.lastname: Frosch
authors.forename: Oliver
authors.initials: O
authors.lastname: Kurzai
mesh_terms: D016667:Bacterial Capsules / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007378:Interleukins / Q000276:immunology / Q000378:metabolism*; D009345:Neisseria meningitidis / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*
chemical_list: D007378:Interleukins; D051117:Scavenger Receptors, Class A; D014409:Tumor Necrosis Factor-alpha