RIG-I detects infection with liveListeriaby sensing secreted bacterial nucleic acids

Abstract

Immunity against infection with Listeria monocytogenes is not achieved from innate immune stimulation by contact with killed but requires viable Listeria gaining access to the cytosol of infected cells. It has remained ill‐defined how such immune sensing of live Listeria occurs. Here, we report that efficient cytosolic immune sensing requires access of nucleic acids derived from live Listeria to the cytoplasm of infected cells. We found that Listeria released nucleic acids and that such secreted bacterial RNA/DNA was recognized by the cytosolic sensors RIG‐I, MDA5 and STING thereby triggering interferon β production. Secreted Listeria nucleic acids also caused RIG‐I‐dependent IL‐1β‐production and inflammasome activation. The signalling molecule CARD9 contributed to IL‐1β production in response to secreted nucleic acids. In conclusion, cytosolic recognition of secreted bacterial nucleic acids by RIG‐I provides a mechanistic explanation for efficient induction of immunity by live bacteria.

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).…”

Identification of TLR10 as a Key Mediator of the Inflammatory Response to Listeria monocytogenes in Intestinal Epithelial Cells and Macrophages

“…L. monocytogenes infection has also been shown to induce a type I IFN response, potentially mediated by TLR2 and the adaptor protein TRIF in peritoneal macrophages (13). Most recently the IFN-b response has been shown to be triggered by nucleic acids released from L. monocytogenes acting through the intracellular sensor RIG-I (14). Previous in vitro mouse studies have predominantly used i.p.…”

Higher antiviral response of RIG-I through enhancing RIG-I/MAVS-mediated signaling by its long insertion variant in zebrafish

“…Kong et al (2009) found that RIG-I À/À mice exhibited a reduced threshold to the challenge of lethal bacteria Edwardsiella coli [16]. Abdullah et al (2012) reported that RIG-I was able to detect live Listeria monocytogenes infection by recognizing secreted bacterial RNA/DNA [15]. On the other hand, studies in fish showed that RIG-I-mediated signaling pathway in grass carp and channel catfish was induced by bacterial components (LPS and PGN) or live bacteria Edwardsiella ictaluri infection [18,21].…”

“…The phosphorylated IRF-3/7 are then able to translocate into the nucleus and induce the production of type I IFNs and IFN-stimulated genes (ISGs), contributing to host antiviral immunity [14]. Recently, it has also been reported that RIG-I may recognize secreted bacterial nucleic acids in cytoplasm and function in antibacterial response, in addition to the previously described antiviral roles [15,16].…”