title: Salmonella virulence factor SipB induces activation and release of IL-18 in human dendritic cells.
abstract: Interleukin-18 (IL-18) plays an important role in innate and acquired immunity, in particular against intracellular pathogens. However, little is known about the microbial factors that trigger IL-18 secretion by dendritic cells (DCs). To determine the influence of bacterial virulence factors on the activation and release of IL-18, we infected human monocyte-derived DCs with virulence mutants of the facultative intracellular pathogen Salmonella typhimurium. Our results show that infection by S. typhimurium causes caspase-1-dependent activation of IL-18 and triggers the release of IL-18 in human DCs. The secretion of IL-18 by the DCs was closely correlated with the ability of the S. typhimurium strains to induce apoptosis. We demonstrate that activation and release of IL-18 are blocked by mutations in the Salmonella sipB gene, which encodes a virulence factor that activates caspase-1 to induce apoptosis. These findings indicate that the activation and release of IL-18 induced by bacterial virulence factors may represent one component of innate immunity against the intracellular bacteria.
authors.affiliation: Division of Pneumology, University Hospital of Geneva, Switzerland. dreher@dim.hcuge.ch
authors.forename: Donatus
authors.initials: D
authors.lastname: Dreher
authors.forename: Menno
authors.initials: M
authors.lastname: Kok
authors.forename: Carolina
authors.initials: C
authors.lastname: Obregon
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Kiama
authors.forename: Peter
authors.initials: P
authors.lastname: Gehr
authors.forename: Laurent P
authors.initials: LP
authors.lastname: Nicod
mesh_terms: D017209:Apoptosis; D001426:Bacterial Proteins / Q000276:immunology*; D020170:Caspase 1 / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D020382:Interleukin-18 / Q000378:metabolism*; D008565:Membrane Proteins / Q000276:immunology*; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D020382:Interleukin-18; D008565:Membrane Proteins; C094579:invasion protein B, Salmonella typhimurium; D007371:Interferon-gamma; D020170:Caspase 1