451. Salmonella virulence factor SipB induces activation and release of IL-18 in human dendritic cells.
- Author
-
Dreher D, Kok M, Obregon C, Kiama SG, Gehr P, and Nicod LP
- Subjects
- Apoptosis, Caspase 1 immunology, Dendritic Cells microbiology, Humans, Interferon-gamma immunology, Salmonella typhimurium genetics, Salmonella typhimurium pathogenicity, Virulence, Bacterial Proteins immunology, Dendritic Cells immunology, Interleukin-18 metabolism, Membrane Proteins immunology, Salmonella typhimurium immunology
- 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.
- Published
- 2002