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dc.contributor.authorFrantz, Renate
dc.contributor.authorTeubner, Lisa
dc.contributor.authorSchultze, Tilman
dc.contributor.authorLa Pietra, Luigi
dc.contributor.authorMüller, Christin
dc.contributor.authorGwozdzinski, Konrad
dc.contributor.authorPillich, Helena
dc.contributor.authorHain, Torsten
dc.contributor.authorWeber-Gerlach, Michaela
dc.contributor.authorPanagiotidis, Georgios-Dimitrios
dc.contributor.authorMostafa, Ahmed
dc.contributor.authorWeber, Friedemann
dc.contributor.authorRohde, Manfred
dc.contributor.authorPleschka, Stephan
dc.contributor.authorChakraborty, Trinad
dc.contributor.authorAbu Mraheil, Mobarak
dc.date.accessioned2019-10-29T11:41:16Z
dc.date.available2019-10-29T11:41:16Z
dc.date.issued2019-10-08
dc.identifier.citationMBio. 2019 Oct 8;10(5). pii: mBio.01223-19. doi: 10.1128/mBio.01223-19en_US
dc.identifier.issn2150-7511
dc.identifier.pmid31594810
dc.identifier.doi10.1128/mBio.01223-19
dc.identifier.urihttp://hdl.handle.net/10033/621995
dc.description.abstractCellular 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.en_US
dc.language.isoenen_US
dc.publisherASMen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectListeria monocytogenesen_US
dc.subjectsecreted RNAen_US
dc.subjecttype I IFNen_US
dc.titleThe secRNome of Listeria monocytogenes Harbors Small Noncoding RNAs That Are Potent Inducers of Beta Interferon.en_US
dc.typeArticleen_US
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalMBIOen_US
refterms.dateFOA2019-10-29T11:41:17Z
dc.source.journaltitlemBio


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