Human alveolar macrophages infected by virulent bacteria expressing SipB are a major source of active interleukin-18.

Détails

ID Serval
serval:BIB_9ADB06633946
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Human alveolar macrophages infected by virulent bacteria expressing SipB are a major source of active interleukin-18.
Périodique
Infection and immunity
Auteur(s)
Obregon C., Dreher D., Kok M., Cochand L., Kiama G.S., Nicod L.P.
ISSN
0019-9567
Statut éditorial
Publié
Date de publication
2003
Peer-reviewed
Oui
Volume
71
Numéro
8
Pages
4382-8
Langue
anglais
Notes
Publication types: In Vitro ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Recent publications have demonstrated that the protease caspase-1 is responsible for the processing of pro-interleukin 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.
Mots-clé
Amino Acid Chloromethyl Ketones/pharmacology, Bacterial Proteins/genetics, Bacterial Proteins/immunology, Base Sequence, Caspase 1/antagonists & inhibitors, Cysteine Proteinase Inhibitors/pharmacology, DNA/genetics, Dendritic Cells/immunology, Gene Expression, Genes, Bacterial, Humans, Interleukin-18/biosynthesis, Interleukin-18/genetics, Macrophages/immunology, Macrophages, Alveolar/immunology, Macrophages, Alveolar/microbiology, Membrane Proteins/genetics, Membrane Proteins/immunology, Mutation, Salmonella typhimurium/genetics, Salmonella typhimurium/immunology, Virulence/genetics, Virulence/immunology
Pubmed
Web of science
Open Access
Oui
Création de la notice
12/02/2010 16:51
Dernière modification de la notice
08/05/2019 22:35
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