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dc.contributor.authorLawless, Nathan*
dc.contributor.authorReinhardt, Timothy A.*
dc.contributor.authorBryan, Kenneth*
dc.contributor.authorBaker, Mike*
dc.contributor.authorPesch, Bruce*
dc.contributor.authorZimmerman, Duane*
dc.contributor.authorZuelke, Kurt*
dc.contributor.authorSonstegard, Tad*
dc.contributor.authorO'Farrelly, Cliona*
dc.contributor.authorLippolis, John D.*
dc.contributor.authorLynn, David J*
dc.date.accessioned2015-05-27T11:26:19Z
dc.date.available2015-05-27T11:26:19Z
dc.date.issued2014-01-27
dc.identifier.citationNathan Lawless, Timothy A. Reinhardt, Kenneth Bryan, Mike Baker, Bruce Pesch, Duane Zimmerman, Kurt Zuelke, Tad Sonstegard, Cliona O'Farrelly, John D. Lippolis and David J. Lynn. MicroRNA Regulation of Bovine Monocyte Inflammatory and Metabolic Networks in an In Vivo Infection Model. G3: Genes|Genomes|Genetics published on January 27, 2014 as doi:10.1534/g3.113.009936en_GB
dc.identifier.urihttp://hdl.handle.net/11019/799
dc.descriptionpeer-revieweden_GB
dc.description.abstractBovine mastitis is an inflammation-driven disease of the bovine mammary gland that costs the global dairy industry several billion dollars per annum. Because disease susceptibility is a multi-factorial complex phenotype, an integrative biology approach is required to dissect the molecular networks involved. Here, we report such an approach, using next generation sequencing combined with advanced network and pathway biology methods to simultaneously profile mRNA and miRNA expression at multiple time-points (0, 12, 24, 36 and 48h) in both milk and blood FACS-isolated CD14+ monocytes from animals infected in vivo with Streptococcus uberis. More than 3,700 differentially expressed (DE) genes were identified in milk-isolated monocytes (MIMs), a key immune cell recruited to the site of infection during mastitis. Up-regulated genes were significantly enriched for inflammatory pathways, while down-regulated genes were enriched for non-glycolytic metabolic pathways. Monocyte transcriptional changes in the blood, however, were more subtle but highlighted the impact of this infection systemically. Genes up-regulated in blood-isolated-monocytes (BIMs) showed a significant association with interferon and chemokine signalling. Furthermore, twenty-six miRNAs were differentially expressed in MIMs and three in BIMs. Pathway analysis revealed that predicted targets of down-regulated miRNAs were highly enriched for roles in innate immunity (FDR < 3.4E-8) in particular TLR signalling, while up-regulated miRNAs preferentially targeted genes involved in metabolism. We conclude that during S. uberis infection miRNAs are key amplifiers of monocyte inflammatory response networks and repressors of several metabolic pathways.en_GB
dc.description.sponsorshipThis study was funded in part by Teagasc RMIS 6018 and United States Department of Agriculture ARS funding 3625-32000-102-00. NL is supported by a Teagasc Walsh Fellowship.en_GB
dc.language.isoenen_GB
dc.publisherGenetics Society of Americaen_GB
dc.relation.ispartofseriesG3 Genes Geomes Genetics;
dc.subjectInfectionen_GB
dc.subjectInnate immunityen_GB
dc.subjectRNAseqen_GB
dc.subjectTranscriptional networksen_GB
dc.subjectMicroRNAen_GB
dc.subjectComplex geneticsen_GB
dc.subjectToleranceen_GB
dc.subjectComplex immunityen_GB
dc.subjectResistanceen_GB
dc.titleMicroRNA regulation of bovine monocyte inflammatory and metabolic networks in an in vivo infection model.en_GB
dc.typeArticleen_GB
dc.identifier.rmisGe-AB-6018
dc.identifier.doihttp://dx.doi.org/10.1534/g3.113.009936
dc.contributor.sponsorTeagasc Walsh Fellowship Programme
dc.contributor.sponsorUS Department of Agriculture
dc.contributor.sponsorTeagasc
dc.contributor.sponsorGrantNumber3625-32000-102-00
refterms.dateFOA2018-01-12T08:12:54Z


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