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* Division of Pneumology, University Hospital of Geneva, Switzerland;
Department of Genetics and Microbiology and Department of Medical Biochemistry, University of Geneva, Switzerland;
Institute of Anatomy, University of Berne, Switzerland; and
Department of Veterinary Anatomy, University of Nairobi, Kenya
Correspondence: Dr. Donatus Dreher, Division of Pneumology, Centre Médical Universitaire, 1, rue Michel-Servet, 1211 Geneva-4, Switzerland. E-mail: dreher{at}dim.hcuge.ch
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.
Key Words: antigen-presenting cells • cytokines • innate immunity • bacteria • host defense
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