Listeria monocytogenes induces IFNβ expression through an IFI16‐, cGAS‐ and STING‐dependent pathway

• DOI: 10.15252/embj.201488029
• Publication Date: 2014-06-27T03:09:35Z
• Authors: Kathrine Hansen; Thaneas Prabakaran; Anders Laustsen; Sofie E Jørgensen; Stine H Rahbæk; Søren B Jensen; Rikke Nielsen; Jess H Leber; Thomas Decker; Kristy A Horan; Martin R Jakobsen; Søren R Paludan
• Keywords: DNA, Bacterial; 0301 basic medicine; Protein Serine-Threonine Kinases; DENDRITIC CELLS; DI-GMP; ACTIVATION; 301902 Immunologie; Mice; 03 medical and health sciences; Cytosol; I INTERFERON RESPONSE; SDG 3 - Good Health and Well-being; Animals; Humans; Listeriosis; interferon beta; innate immunity; Cells, Cultured; Macrophages; Membrane Proteins; Nuclear Proteins; CYCLIC GMP-AMP; CYTOSOLIC SURVEILLANCE PATHWAY; Interferon-beta; AIM2 INFLAMMASOME; Phosphoproteins; INTRACELLULAR DNA; Listeria monocytogenes; Nucleotidyltransferases; 3. Good health; Mice, Inbred C57BL; SDG 3 – Gesundheit und Wohlergehen; Gene Knockdown Techniques; Host-Pathogen Interactions; 2ND-MESSENGER; 301902 Immunology; INNATE IMMUNE SENSOR; Signal Transduction

AbstractListeria 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.