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.
Keywords:
Listeria monocytogenes; innate immunity; interferon beta.
© 2014 The Authors.
MeSH terms
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Animals
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Cells, Cultured
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Cytosol / metabolism
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DNA, Bacterial / metabolism
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Gene Knockdown Techniques
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Host-Pathogen Interactions*
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Humans
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Interferon-beta / metabolism*
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Listeria monocytogenes / genetics
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Listeria monocytogenes / metabolism
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Listeria monocytogenes / pathogenicity*
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Listeriosis / metabolism
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Listeriosis / microbiology
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Macrophages / metabolism
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Macrophages / microbiology
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Mice
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Mice, Inbred C57BL
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Nucleotidyltransferases / genetics
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Nucleotidyltransferases / metabolism*
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Phosphoproteins / genetics
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Phosphoproteins / metabolism*
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Protein Serine-Threonine Kinases / metabolism
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Signal Transduction
Substances
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DNA, Bacterial
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Membrane Proteins
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Nuclear Proteins
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Phosphoproteins
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STING1 protein, human
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IFI16 protein, human
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Interferon-beta
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Protein Serine-Threonine Kinases
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TBK1 protein, human
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Nucleotidyltransferases
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cGAS protein, human