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Imaging of In Situ Interferon Gamma Production in the Mouse Spleen following Listeria monocytogenes Infection
Published on: July 16, 2019
Listeria monocytogenes induces IFNβ expression through an IFI16-, cGAS- and STING-dependent pathway
Kathrine Hansen1, Thaneas Prabakaran1, Anders Laustsen1
1Department of Biomedicine, Aarhus University, Aarhus, Denmark Aarhus Research Centre for Innate Immunology, Aarhus University, Aarhus, Denmark.
Abstract:
Listeria monocytogenes is a gram-positive facultative intracellular bacterium, which replicates in the cytoplasm of myeloid cells. Interferon β (IFNβ) has been reported to play an important role in the mechanisms underlying Listeria disease. Although studies in murine cells have proposed the bacteria-derived cyclic-di-AMP to be the key bacterial immunostimulatory molecule, the mechanism for IFNβ expression during L. monocytogenes infection in human myeloid cells remains unknown. Here we report that in human macrophages, Listeria DNA rather than cyclic-di-AMP is stimulating the IFN response via a pathway dependent on the DNA sensors IFI16 and cGAS as well as the signalling adaptor molecule STING. Thus, Listeria DNA is a major trigger of IFNβ expression in human myeloid cells and is sensed to activate a pathway dependent on IFI16, cGAS and STING.
Insights
In human myeloid cells, Listeria DNA, not cyclic-di-AMP, triggers Interferon β (IFNβ) production. This response is mediated by IFI16, cGAS, and STING, revealing a key pathway in Listeria infection immunity.
Area of Science:
- Immunology
- Microbiology
- Cellular Biology
Background:
- Listeria monocytogenes is a gram-positive bacterium that infects myeloid cells.
- Interferon β (IFNβ) is crucial in Listeria disease pathogenesis.
- The mechanism of IFNβ induction in human myeloid cells during Listeria infection is not fully understood.
Purpose of the Study:
- To elucidate the mechanism of IFNβ expression in human myeloid cells upon Listeria monocytogenes infection.
- To identify the bacterial molecules and host sensors involved in initiating the IFNβ response.
Main Methods:
- Human macrophages were infected with Listeria monocytogenes.
- Investigated the role of cyclic-di-AMP versus bacterial DNA in triggering the IFN response.
- Utilized genetic and molecular techniques to assess the involvement of IFI16, cGAS, and STING pathways.
Main Results:
- Listeria DNA, not cyclic-di-AMP, was identified as the primary stimulus for IFNβ production in human macrophages.
- The IFN response was dependent on the DNA sensors IFI16 and cGAS.
- The signaling adaptor molecule STING was essential for mediating the downstream signaling cascade.
Conclusions:
- Bacterial DNA is a critical trigger for IFNβ expression in human myeloid cells during Listeria infection.
- The IFI16-cGAS-STING pathway is essential for sensing Listeria DNA and activating the innate immune response.
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