The secRNome of <named-content content-type="genus-species">Listeria monocytogenes</named-content> Harbors Small Noncoding RNAs That Are Potent Inducers of Beta Interferon
ABSTRACT Cellular sensing of bacterial RNA is increasingly recognized as a determinant of host-pathogen interactions. The intracellular pathogen Listeria monocytogenes induces high levels of type I interferons (alpha/beta interferons [IFN-α/β]) to create a growth-permissive microenvironment during i...
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American Society for Microbiology
2019
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oai:doaj.org-article:07b84c71fa274bd1a66c3743af524a092021-11-15T15:59:41ZThe secRNome of <named-content content-type="genus-species">Listeria monocytogenes</named-content> Harbors Small Noncoding RNAs That Are Potent Inducers of Beta Interferon10.1128/mBio.01223-192150-7511https://doaj.org/article/07b84c71fa274bd1a66c3743af524a092019-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01223-19https://doaj.org/toc/2150-7511ABSTRACT Cellular sensing of bacterial RNA is increasingly recognized as a determinant of host-pathogen interactions. The intracellular pathogen Listeria monocytogenes induces high levels of type I interferons (alpha/beta interferons [IFN-α/β]) to create a growth-permissive microenvironment during infection. We previously demonstrated that RNAs secreted by L. monocytogenes (comprising the secRNome) are potent inducers of IFN-β. We determined the composition and diversity of the members of the secRNome and found that they are uniquely enriched for noncoding small RNAs (sRNAs). Testing of individual sRNAs for their ability to induce IFN revealed several sRNAs with this property. We examined ril32, an intracellularly expressed sRNA that is highly conserved for the species L. monocytogenes and that was the most potent inducer of IFN-β expression of all the sRNAs tested in this study, in more detail. The rli32-induced IFN-β response is RIG-I (retinoic acid inducible gene I) dependent, and cells primed with rli32 inhibit influenza virus replication. We determined the rli32 motif required for IFN induction. rli32 overproduction promotes intracellular bacterial growth, and a mutant lacking rli32 is restricted for intracellular growth in macrophages. rli32-overproducing bacteria are resistant to H2O2 and exhibit both increased catalase activity and changes in the cell envelope. Comparative transcriptome sequencing (RNA-Seq) analysis indicated that ril32 regulates expression of the lhrC locus, previously shown to be involved in cell envelope stress. Inhibition of IFN-β signaling by ruxolitinib reduced rli32-dependent intracellular bacterial growth, indicating a link between induction of the interferon system and bacterial physiology. rli32 is, to the best of our knowledge, the first secreted individual bacterial sRNA known to trigger the induction of the type I IFN response. IMPORTANCE Interferons are potent and broadly acting cytokines that stimulate cellular responses to nucleic acids of unusual structures or locations. While protective when induced following viral infections, the induction of interferons is detrimental to the host during L. monocytogenes infection. Here, we identify specific sRNAs, secreted by the bacterium, with the capacity to induce type I IFN. Further analysis of the most potent sRNA, rli32, links the ability to induce RIG-I-dependent induction of the type I IFN response to the intracellular growth properties of the bacterium. Our findings emphasize the significance of released RNA for Listeria infection and shed light on a compartmental strategy used by an intracellular pathogen to modulate host responses to its advantage.Renate FrantzLisa TeubnerTilman SchultzeLuigi La PietraChristin MüllerKonrad GwozdzinskiHelena PillichTorsten HainMichaela Weber-GerlachGeorgios-Dimitrios PanagiotidisAhmed MostafaFriedemann WeberManfred RohdeStephan PleschkaTrinad ChakrabortyMobarak Abu MraheilAmerican Society for MicrobiologyarticleListeria monocytogenestype I IFNsecreted RNAMicrobiologyQR1-502ENmBio, Vol 10, Iss 5 (2019) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Listeria monocytogenes type I IFN secreted RNA Microbiology QR1-502 |
| spellingShingle |
Listeria monocytogenes type I IFN secreted RNA Microbiology QR1-502 Renate Frantz Lisa Teubner Tilman Schultze Luigi La Pietra Christin Müller Konrad Gwozdzinski Helena Pillich Torsten Hain Michaela Weber-Gerlach Georgios-Dimitrios Panagiotidis Ahmed Mostafa Friedemann Weber Manfred Rohde Stephan Pleschka Trinad Chakraborty Mobarak Abu Mraheil The secRNome of <named-content content-type="genus-species">Listeria monocytogenes</named-content> Harbors Small Noncoding RNAs That Are Potent Inducers of Beta Interferon |
| description |
ABSTRACT Cellular sensing of bacterial RNA is increasingly recognized as a determinant of host-pathogen interactions. The intracellular pathogen Listeria monocytogenes induces high levels of type I interferons (alpha/beta interferons [IFN-α/β]) to create a growth-permissive microenvironment during infection. We previously demonstrated that RNAs secreted by L. monocytogenes (comprising the secRNome) are potent inducers of IFN-β. We determined the composition and diversity of the members of the secRNome and found that they are uniquely enriched for noncoding small RNAs (sRNAs). Testing of individual sRNAs for their ability to induce IFN revealed several sRNAs with this property. We examined ril32, an intracellularly expressed sRNA that is highly conserved for the species L. monocytogenes and that was the most potent inducer of IFN-β expression of all the sRNAs tested in this study, in more detail. The rli32-induced IFN-β response is RIG-I (retinoic acid inducible gene I) dependent, and cells primed with rli32 inhibit influenza virus replication. We determined the rli32 motif required for IFN induction. rli32 overproduction promotes intracellular bacterial growth, and a mutant lacking rli32 is restricted for intracellular growth in macrophages. rli32-overproducing bacteria are resistant to H2O2 and exhibit both increased catalase activity and changes in the cell envelope. Comparative transcriptome sequencing (RNA-Seq) analysis indicated that ril32 regulates expression of the lhrC locus, previously shown to be involved in cell envelope stress. Inhibition of IFN-β signaling by ruxolitinib reduced rli32-dependent intracellular bacterial growth, indicating a link between induction of the interferon system and bacterial physiology. rli32 is, to the best of our knowledge, the first secreted individual bacterial sRNA known to trigger the induction of the type I IFN response. IMPORTANCE Interferons are potent and broadly acting cytokines that stimulate cellular responses to nucleic acids of unusual structures or locations. While protective when induced following viral infections, the induction of interferons is detrimental to the host during L. monocytogenes infection. Here, we identify specific sRNAs, secreted by the bacterium, with the capacity to induce type I IFN. Further analysis of the most potent sRNA, rli32, links the ability to induce RIG-I-dependent induction of the type I IFN response to the intracellular growth properties of the bacterium. Our findings emphasize the significance of released RNA for Listeria infection and shed light on a compartmental strategy used by an intracellular pathogen to modulate host responses to its advantage. |
| format |
article |
| author |
Renate Frantz Lisa Teubner Tilman Schultze Luigi La Pietra Christin Müller Konrad Gwozdzinski Helena Pillich Torsten Hain Michaela Weber-Gerlach Georgios-Dimitrios Panagiotidis Ahmed Mostafa Friedemann Weber Manfred Rohde Stephan Pleschka Trinad Chakraborty Mobarak Abu Mraheil |
| author_facet |
Renate Frantz Lisa Teubner Tilman Schultze Luigi La Pietra Christin Müller Konrad Gwozdzinski Helena Pillich Torsten Hain Michaela Weber-Gerlach Georgios-Dimitrios Panagiotidis Ahmed Mostafa Friedemann Weber Manfred Rohde Stephan Pleschka Trinad Chakraborty Mobarak Abu Mraheil |
| author_sort |
Renate Frantz |
| title |
The secRNome of <named-content content-type="genus-species">Listeria monocytogenes</named-content> Harbors Small Noncoding RNAs That Are Potent Inducers of Beta Interferon |
| title_short |
The secRNome of <named-content content-type="genus-species">Listeria monocytogenes</named-content> Harbors Small Noncoding RNAs That Are Potent Inducers of Beta Interferon |
| title_full |
The secRNome of <named-content content-type="genus-species">Listeria monocytogenes</named-content> Harbors Small Noncoding RNAs That Are Potent Inducers of Beta Interferon |
| title_fullStr |
The secRNome of <named-content content-type="genus-species">Listeria monocytogenes</named-content> Harbors Small Noncoding RNAs That Are Potent Inducers of Beta Interferon |
| title_full_unstemmed |
The secRNome of <named-content content-type="genus-species">Listeria monocytogenes</named-content> Harbors Small Noncoding RNAs That Are Potent Inducers of Beta Interferon |
| title_sort |
secrnome of <named-content content-type="genus-species">listeria monocytogenes</named-content> harbors small noncoding rnas that are potent inducers of beta interferon |
| publisher |
American Society for Microbiology |
| publishDate |
2019 |
| url |
https://doaj.org/article/07b84c71fa274bd1a66c3743af524a09 |
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