title: Listeria monocytogenes induces IFNβ expression through an IFI16-, cGAS- and STING-dependent pathway.
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.
authors: Department of Biomedicine, Aarhus University, Aarhus, Denmark Aarhus Research Centre for Innate Immunology, Aarhus University, Aarhus, Denmark.
authors: Kathrine
authors: K
authors: Hansen
authors: Department of Biomedicine, Aarhus University, Aarhus, Denmark Aarhus Research Centre for Innate Immunology, Aarhus University, Aarhus, Denmark.
authors: Thaneas
authors: T
authors: Prabakaran
authors: Department of Biomedicine, Aarhus University, Aarhus, Denmark Aarhus Research Centre for Innate Immunology, Aarhus University, Aarhus, Denmark.
authors: Anders
authors: A
authors: Laustsen
authors: Department of Biomedicine, Aarhus University, Aarhus, Denmark Aarhus Research Centre for Innate Immunology, Aarhus University, Aarhus, Denmark.
authors: Sofie E
authors: SE
authors: Jørgensen
authors: Department of Biomedicine, Aarhus University, Aarhus, Denmark Aarhus Research Centre for Innate Immunology, Aarhus University, Aarhus, Denmark.
authors: Stine H
authors: SH
authors: Rahbæk
authors: Department of Biomedicine, Aarhus University, Aarhus, Denmark Aarhus Research Centre for Innate Immunology, Aarhus University, Aarhus, Denmark.
authors: Søren B
authors: SB
authors: Jensen
authors: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors: Rikke
authors: R
authors: Nielsen
authors: Department of Microbiology, The University of Chicago, Chicago, IL, USA.
authors: Jess H
authors: JH
authors: Leber
authors: Max F. Perutz Laboratories, Department of Microbiology, Immunobiology and Genetics, University of Vienna, Vienna, Austria.
authors: Thomas
authors: T
authors: Decker
authors: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors: Kristy A
authors: KA
authors: Horan
authors: Department of Biomedicine, Aarhus University, Aarhus, Denmark Aarhus Research Centre for Innate Immunology, Aarhus University, Aarhus, Denmark.
authors: Martin R
authors: MR
authors: Jakobsen
authors: Department of Biomedicine, Aarhus University, Aarhus, Denmark Aarhus Research Centre for Innate Immunology, Aarhus University, Aarhus, Denmark srp@microbiology.au.dk.
authors: Søren R
authors: SR
authors: Paludan
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004269:DNA, Bacterial / Q000378:metabolism; D055785:Gene Knockdown Techniques; D054884:Host-Pathogen Interactions; D006801:Humans; D016899:Interferon-beta / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D008088:Listeriosis / Q000378:metabolism / Q000382:microbiology; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009713:Nucleotidyltransferases / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction; D000099197:STING Protein; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
chemical_list: D004269:DNA, Bacterial; D016899:Interferon-beta; D008565:Membrane Proteins; D009687:Nuclear Proteins; D009713:Nucleotidyltransferases; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; C532857:STING1 protein, human; D000099197:STING Protein; C076700:IFI16 protein, human; C403191:TBK1 protein, human; C578390:cGAS protein, human; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
keywords: Listeria monocytogenes; innate immunity; interferon beta