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Salmonella virulence factor SipB induces activation and release of IL‐18 in human dendritic cells
Author(s) -
Dreher Donatus,
Kok Menno,
Obregon Carolina,
Kiama Stephen G.,
Gehr Peter,
Nicod Laurent P.
Publication year - 2002
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.72.4.743
Subject(s) - virulence , biology , microbiology and biotechnology , innate immune system , secretion , intracellular parasite , intracellular , salmonella , virulence factor , immunity , bacteria , immune system , immunology , gene , biochemistry , genetics
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.