title: RIG-I detects triphosphorylated RNA of Listeria monocytogenes during infection in non-immune cells.
abstract: The innate immune system senses pathogens by pattern recognition receptors in different cell compartments. In the endosome, bacteria are generally recognized by TLRs; facultative intracellular bacteria such as Listeria, however, can escape the endosome. Once in the cytosol, they become accessible to cytosolic pattern recognition receptors, which recognize components of the bacterial cell wall, metabolites or bacterial nucleic acids and initiate an immune response in the host cell. Current knowledge has been focused on the type I IFN response to Listeria DNA or Listeria-derived second messenger c-di-AMP via the signaling adaptor STING. Our study focused on the recognition of Listeria RNA in the cytosol. With the aid of a novel labeling technique, we have been able to visualize immediate cytosolic delivery of Listeria RNA upon infection. Infection with Listeria as well as transfection of bacterial RNA induced a type-I-IFN response in human monocytes, epithelial cells or hepatocytes. However, in contrast to monocytes, the type-I-IFN response of epithelial cells and hepatocytes was not triggered by bacterial DNA, indicating a STING-independent Listeria recognition pathway. RIG-I and MAVS knock-down resulted in abolishment of the IFN response in epithelial cells, but the IFN response in monocytic cells remained unaffected. By contrast, knockdown of STING in monocytic cells reduced cytosolic Listeria-mediated type-I-IFN induction. Our results show that detection of Listeria RNA by RIG-I represents a non-redundant cytosolic immunorecognition pathway in non-immune cells lacking a functional STING dependent signaling pathway.
authors: Institute for Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, University of Bonn, Bonn, Germany.
authors: Cristina Amparo
authors: CA
authors: Hagmann
authors: Anna Maria
authors: AM
authors: Herzner
authors: Zeinab
authors: Z
authors: Abdullah
authors: Thomas
authors: T
authors: Zillinger
authors: Christopher
authors: C
authors: Jakobs
authors: Christine
authors: C
authors: Schuberth
authors: Christoph
authors: C
authors: Coch
authors: Paul G
authors: PG
authors: Higgins
authors: Hilmar
authors: H
authors: Wisplinghoff
authors: Winfried
authors: W
authors: Barchet
authors: Veit
authors: V
authors: Hornung
authors: Gunther
authors: G
authors: Hartmann
authors: Martin
authors: M
authors: Schlee
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism / Q000382:microbiology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D054884:Host-Pathogen Interactions; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis / Q000378:metabolism; D008089:Listeria monocytogenes / Q000378:metabolism*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D010766:Phosphorylation; D012329:RNA, Bacterial / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000099197:STING Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D007370:Interferon Type I; D008565:Membrane Proteins; D012329:RNA, Bacterial; D034741:RNA, Small Interfering; D018168:Receptors, Retinoic Acid; C505371:MAVS protein, human; C437968:PLAAT4 protein, human; C532857:STING1 protein, human; D000099197:STING Protein
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