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.

Microbial Sensing by Toll-Like Receptors and Intracellular Nucleic Acid Sensors

“…RIG-I also recognizes influenza Avirus, measles virus, and Ebola virus (Thompson et al 2011). Listeria monocytogenes actively secretes small RNAs via a SecA2 secretion system, thereby triggering strong RIG-I activation that leads to type I IFN production (Abdullah et al 2012;Hagmann et al 2013). Compared with RIG-I, MDA5 recognizes a different class of viruses, such as Picornaviridae, and MDA5-deficient mice show abrogated type I IFN production in response to EMCV, Theiler's virus, hepatitis C virus, mengovirus, and murine norovirus McCartney et al 2008).…”

NOD1 Participates in the Innate Immune Response Triggered by Hepatitis C Virus Polymerase

“…In addition, NOD2, but not NOD1, appears to directly recognize single-stranded viral RNA (ssRNA) (28). Symmetrically, RIG-I, a classical antiviral PRR, has recently been shown to respond to Listeria monocytogenes RNA (30). These examples illustrate the existence of an extensive cross talk between different classes of innate response signaling pathways (reviewed in reference 16).…”

Bacterial RNA: An Underestimated Stimulus for Innate Immune Responses

“…Among the cytosolic RLRs, MDA5 was identified to initiate antiviral signaling in response to long stretches of viral dsRNA, whereas RIG-I is a sensor of short dsRNA or ssRNA with 592triphosphate termini (13)(14)(15)(16). However, RIG-I also was implicated in the recognition of RNA from Listeria monocytogenes (17,18). Recently discovered cyclic GMP-AMP synthase and absent in melanoma 2 are cytosolic receptors that recognize microbial DNA (19)(20)(21)(22)(23)(24).…”