PMID- 12377944 OWN - NLM STAT- MEDLINE DCOM- 20021115 LR - 20181130 IS - 0741-5400 (Print) IS - 0741-5400 (Linking) VI - 72 IP - 4 DP - 2002 Oct TI - Salmonella virulence factor SipB induces activation and release of IL-18 in human dendritic cells. PG - 743-51 AB - 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. FAU - Dreher, Donatus AU - Dreher D AD - Division of Pneumology, University Hospital of Geneva, Switzerland. dreher@dim.hcuge.ch FAU - Kok, Menno AU - Kok M FAU - Obregon, Carolina AU - Obregon C FAU - Kiama, Stephen G AU - Kiama SG FAU - Gehr, Peter AU - Gehr P FAU - Nicod, Laurent P AU - Nicod LP LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Leukoc Biol JT - Journal of leukocyte biology JID - 8405628 RN - 0 (Bacterial Proteins) RN - 0 (Interleukin-18) RN - 0 (Membrane Proteins) RN - 0 (invasion protein B, Salmonella typhimurium) RN - 82115-62-6 (Interferon-gamma) RN - EC 3.4.22.36 (Caspase 1) SB - IM MH - Apoptosis MH - Bacterial Proteins/*immunology MH - Caspase 1/immunology MH - Dendritic Cells/*immunology/microbiology MH - Humans MH - Interferon-gamma/immunology MH - Interleukin-18/*metabolism MH - Membrane Proteins/*immunology MH - Salmonella typhimurium/genetics/*immunology/pathogenicity MH - Virulence EDAT- 2002/10/16 04:00 MHDA- 2002/11/26 04:00 CRDT- 2002/10/16 04:00 PHST- 2002/10/16 04:00 [pubmed] PHST- 2002/11/26 04:00 [medline] PHST- 2002/10/16 04:00 [entrez] PST - ppublish SO - J Leukoc Biol. 2002 Oct;72(4):743-51.