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: Cristina Amparo Hagmann, Anna Maria Herzner, Zeinab Abdullah, Thomas Zillinger, Christopher Jakobs, Christine Schuberth, Christoph Coch, Paul G Higgins, Hilmar Wisplinghoff, Winfried Barchet, Veit Hornung, Gunther Hartmann, Martin Schlee
• Journal: PloS one (PLoS One) Vol. 8 Issue 4 Pg. e62872 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23653683 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• Interferon Type I
• MAVS protein, human
• Membrane Proteins
• PLAAT4 protein, human
• RNA, Bacterial
• RNA, Small Interfering
• Receptors, Retinoic Acid
• STING1 protein, human

Topics

• Adaptor Proteins, Signal Transducing (antagonists & inhibitors, genetics, metabolism)
• Cells, Cultured
• Cytosol (metabolism, microbiology)
• Epithelial Cells (cytology, metabolism, microbiology)
• Gene Expression Regulation
• Gene Knockdown Techniques
• Hepatocytes (cytology, metabolism, microbiology)
• Host-Pathogen Interactions
• Humans
• Interferon Type I (biosynthesis, metabolism)
• Listeria monocytogenes (metabolism)
• Membrane Proteins (antagonists & inhibitors, genetics, metabolism)
• Monocytes (cytology, metabolism, microbiology)
• Phosphorylation
• RNA, Bacterial (genetics, metabolism)
• RNA, Small Interfering (genetics, metabolism)
• Receptors, Retinoic Acid (antagonists & inhibitors, genetics, metabolism)
• Signal Transduction