Human alveolar macrophages infected by virulent bacteria expressing SipB are a major source of active interleukin-18
Date
2003Author
Obregon, Carolina
Dreher, Donatus
Kok, Menno
Cochand, Laurence
Kiama, S G
Nicod, Laurent P.
Type
ArticleLanguage
enMetadata
Show full item recordAbstract
Recent publications have demonstrated that the protease caspase-1 is responsible for the processing of prointerleukin
18 (IL-18) into the active form. Studies on cell lines and murine macrophages have shown that the
bacterial invasion factor SipB activates caspase-1, triggering cell death. Thus, we investigated the role of SipB
in the activation and release of IL-18 in human alveolar macrophages (AM), which are the first line of defense
against inhaled pathogens. Under steady-state conditions, AM are a more important source of IL-18 than are
dendritic cells (DC) and monocytes. Cytokine production by AM and DC was compared after both types of cells
had been infected with a virulent strain of Salmonella enterica serovar Typhimurium and an isogenic sipB
mutant, which were used as an infection model. Infection with virulent Salmonella led to marked cell death with
features of apoptosis while both intracellular activation and release of IL-18 were demonstrated. In contrast,
the sipB mutant did not induce such cell death or the release of active IL-18. The specific caspase-1 inhibitor
Ac-YVAD-CMK blocked the early IL-18 release in AM infected with the virulent strain. However, the type of
Salmonella infection did not differentially regulate IL-18 gene expression. We concluded that the bacterial
virulence factor SipB plays an essential posttranslational role in the intracellular activation of IL-18 and the
release of the cytokine in human AM
Publisher
Department of Veterinary Anatomy, University of Nairobi, Division of Pneumology, University Hospital of Geneva Department of Genetics and Microbiology, University of Geneva,