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Updated: May 29, 2026
Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
Published on: May 22, 2014
Francisella infection triggers activation of the AIM2 inflammasome in murine dendritic cells
Kamila Belhocine1, Denise M Monack
1Department of Microbiology and Immunology, Stanford School of Medicine, Stanford University, Stanford, CA 94305, USA.
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.
Insights
Francisella novicida activates the AIM2 inflammasome in dendritic cells, leading to cell death. This process may help clear the bacteria and protect the host from tularemia.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Francisella tularensis causes tularemia, a severe disease.
- In macrophages, Francisella replicates in the cytosol, triggering the AIM2 inflammasome.
- Dendritic cells are also infected during aerosol transmission.
Purpose of the Study:
- To investigate Francisella novicida's interaction with dendritic cells.
- To determine if Francisella activates the AIM2 inflammasome in dendritic cells.
- To elucidate the role of the Francisella Pathogenicity Island and IFN-β in this response.
Main Methods:
- Infection of bone marrow-derived dendritic cells (BMDC) with Francisella novicida.
- Analysis of bacterial escape, replication, and inflammasome activation (IL-1β release, cell death).
- Assessment of AIM2 binding, Francisella Pathogenicity Island requirement, and IFN-β signaling.
Main Results:
- Francisella novicida escapes into the cytosol of BMDC and replicates rapidly.
- AIM2 inflammasome activation occurs in BMDC, leading to IL-1β release and cell death.
- The Francisella Pathogenicity Island is essential for these events; IFN-β signaling is partially required.
Conclusions:
- Francisella novicida induces AIM2 inflammasome activation and inflammatory cell death in dendritic cells.
- This response may serve to eliminate the bacterial replicative niche and protect the host.
- Dendritic cells play a critical role in the innate immune response to Francisella infection.
