Salmonella virulence factor SipB induces activation and release of IL-18 in human dendritic cells.
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.
Dreher
Donatus
D
Division of Pneumology, University Hospital of Geneva, Switzerland. dreher@dim.hcuge.ch
Kok
Menno
M
Obregon
Carolina
C
Kiama
Stephen G
SG
Gehr
Peter
P
Nicod
Laurent P
LP
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
D001426:Bacterial Proteins; D020382:Interleukin-18; D008565:Membrane Proteins; C094579:invasion protein B, Salmonella typhimurium; D007371:Interferon-gamma; D020170:Caspase 1