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dc.contributor.authorCorr, Sineaden
dc.contributor.authorO'Neill, Lukeen
dc.contributor.authorJohnston, Danielen
dc.date.accessioned2017-09-21T10:29:03Z
dc.date.available2017-09-21T10:29:03Z
dc.date.issued2017en
dc.date.submitted2017en
dc.identifier.citationJohnston DGW, Kearney J, Zas??ona Z, Williams MA, O'Neill LAJ, Corr SC., MicroRNA-21 Limits Uptake of Listeria monocytogenes by Macrophages to Reduce the Intracellular Niche and Control Infection., Frontiers in cellular and infection microbiology, 7, 2017, 201en
dc.identifier.issn2235-2988en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/81810
dc.descriptionPUBLISHEDen
dc.description.abstractMiRNAs are important post-transcriptional regulators of gene expression. MiRNA expression is a crucial part of host responses to bacterial infection, however there is limited knowledge of their impact on the outcome of infections. We investigated the influence of miR-21 on macrophage responses during infection with Listeria monocytogenes, which establishes an intracellular niche within macrophages. MiR-21 is induced following infection of bone marrow-derived macrophages (BMDMs) with Listeria. MiR-21-/- macrophages display an increased bacterial burden with Listeria at 30 min and 2 h post-infection. This phenotype was reversed by the addition of synthetic miR-21 mimics to the system. To assess the immune response of wildtype (WT) and miR-21-/- macrophages, BMDMs were treated with bacterial LPS or infected with Listeria. There was no difference in IL-10 and IL-6 between WT and miR-21-/- BMDMs in response to LPS or Listeria. TNF-α was increased in miR-21-/- BMDMs stimulated with LPS or Listeria compared to WT macrophages. We next assessed the production of nitric oxide (NO), a key bactericidal factor in Listeria infection. There was no significant difference in NO production between WT and miR-21-/- cells, indicating that the increased bacterial burden may not be due to impaired killing. As the increased bacterial load was observed early following infection (30 min), we questioned whether this is due to differences in uptake of Listeria by WT and miR-21-/- macrophages. We show that miR-21-deficiency enhances uptake of FITC-dextran and FITC-Escherichia coli bioparticles by macrophages. The previously observed Listeria burden phenotype was ablated by pre-treatment of cells with the actin polymerization inhibitor cytochalasin-D. From analysis of miR-21 targets, we selected the pro-phagocytic regulators myristoylated alanine-rich C-kinase substrate (MARCKS) and Ras homolog gene family, member B (RhoB) for further investigation. MARCKS and RhoB are increased in miR-21-/- BMDMs, correlating with increased uptake of Listeria. Finally, intra-peritoneal infection of mice with Listeria led to increased bacterial burden in livers of miR-21-/- mice compared to WT mice. These findings suggest a possible role for miR-21 in regulation of phagocytosis during infection, potentially by repression of MARCKS and RhoB, thus serving to limit the availability of the intracellular niche of pathogens like L. monocytogenes.en
dc.description.sponsorshipScience Foundation Ireland 11/SIRG/B2099en
dc.format.extent201en
dc.language.isoenen
dc.relation.ispartofseriesFrontiers in cellular and infection microbiologyen
dc.relation.ispartofseries7en
dc.rightsYen
dc.subjectListeria, macrophage, miR-21, miRNA, phaocytosisen
dc.titleMicroRNA-21 Limits Uptake of Listeria monocytogenes by Macrophages to Reduce the Intracellular Niche and Control Infection.en
dc.typeJournal Articleen
dc.contributor.sponsorScience Foundation Ireland (SFI)en
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/corrscen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/djohnsten
dc.identifier.peoplefinderurlhttp://people.tcd.ie/laoneillen
dc.identifier.rssinternalid176037en
dc.identifier.doihttp://dx.doi.org/10.3389/fcimb.2017.00201en
dc.rights.ecaccessrightsopenAccess
dc.contributor.sponsorGrantNumber11/SIRG/B2099en
dc.subject.TCDThemeImmunology, Inflammation & Infectionen
dc.identifier.orcid_id0000-0001-9930-5039en


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