title: Francisella infection triggers activation of the AIM2 inflammasome in murine dendritic cells.
abstract: The intracellular bacterium Francisella tularensis is the causative agent of tularemia, a potentially fatal disease. In macrophages, Francisella escapes the initial phagosome and replicates in the cytosol, where it is detected by the cytosolic DNA sensor AIM2 leading to activation of the AIM2 inflammasome. However, during aerosol infection, Francisella is also taken up by dendritic cells. In this study, we show that Francisella novicida escapes into the cytosol of bone marrow-derived dendritic cells (BMDC) where it undergoes rapid replication. We show that F. novicida activates the AIM2 inflammasome in BMDC, causing release of large amounts of IL-1β and rapid host cell death. The Francisella Pathogenicity Island is required for bacterial escape and replication and for inflammasome activation in dendritic cells. In addition, we show that bacterial DNA is bound by AIM2, which leads to inflammasome assembly in infected dendritic cells. IFN-β is upregulated in BMDC following Francisella infection, and the IFN-β signalling pathway is partially required for inflammasome activation in this cell type. Taken together, our results demonstrate that F. novicida induces inflammasome activation in dendritic cells. The resulting inflammatory cell death may be beneficial to remove the bacterial replicative niche and protect the host.
authors: Department of Microbiology and Immunology, Stanford School of Medicine, Stanford University, Stanford, CA 94305, USA.
authors: Kamila
authors: K
authors: Belhocine
authors: Denise M
authors: DM
authors: Monack
mesh_terms: D000818:Animals; D016923:Cell Death; D002478:Cells, Cultured; D003600:Cytosol / Q000382:microbiology; D004269:DNA, Bacterial / Q000378:metabolism; D004268:DNA-Binding Proteins; D003713:Dendritic Cells / Q000276:immunology*; D005603:Francisella / Q000276:immunology* / Q000472:pathogenicity; D044404:Genomic Islands; D058847:Inflammasomes / Q000276:immunology*; D016899:Interferon-beta / Q000378:metabolism; D053583:Interleukin-1beta / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D015398:Signal Transduction; D014406:Tularemia / Q000276:immunology*
chemical_list: C540422:Aim2 protein, mouse; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D009687:Nuclear Proteins; D016899:Interferon-beta