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dc.contributor.authorDuell, Benen_US
dc.contributor.authorCarey, Alisonen_US
dc.contributor.authorTan, CKen_US
dc.contributor.authorCui, Xiangqinen_US
dc.contributor.authorI. Webb, Richarden_US
dc.contributor.authorTotsika, Makrinaen_US
dc.contributor.authorA. Schembri, Marken_US
dc.contributor.authorDerrington, Petraen_US
dc.contributor.authorIrving-Rodgers, Helenen_US
dc.contributor.authorJ. Brooks, Andrewen_US
dc.contributor.authorCripps, Allanen_US
dc.contributor.authorCrowley, Michaelen_US
dc.contributor.authorUlett, Glenen_US
dc.date.accessioned2017-04-24T13:03:42Z
dc.date.available2017-04-24T13:03:42Z
dc.date.issued2012en_US
dc.date.modified2013-06-05T02:39:30Z
dc.identifier.issn1550-6606en_US
dc.identifier.doi10.4049/jimmunol.1101231en_US
dc.identifier.urihttp://hdl.handle.net/10072/47640
dc.description.abstractEarly transcriptional activation events that occur in bladder immediately following bacterial urinary tract infection (UTI) are not well defined. In this study, we describe the whole bladder transcriptome of uropathogenic Escherichia coli (UPEC) cystitis in mice using genome-wide expression profiling to define the transcriptome of innate immune activation stemming from UPEC colonization of the bladder. Bladder RNA from female C57BL/6 mice, analyzed using 1.0 ST-Affymetrix microarrays, revealed extensive activation of diverse sets of innate immune response genes, including those that encode multiple IL-family members, receptors, metabolic regulators, MAPK activators, and lymphocyte signaling molecules. These were among 1564 genes differentially regulated at 2 h postinfection, highlighting a rapid and broad innate immune response to bladder colonization. Integrative systemslevel analyses using InnateDB (http://www.innatedb.com) bioinformatics and ingenuity pathway analysis identified multiple distinct biological pathways in the bladder transcriptome with extensive involvement of lymphocyte signaling, cell cycle alterations, cytoskeletal, and metabolic changes. A key regulator of IL activity identified in the transcriptome was IL-10, which was analyzed functionally to reveal marked exacerbation of cystitis in IL-10-deficient mice. Studies of clinical UTI revealed significantly elevated urinary IL-10 in patients with UPEC cystitis, indicating a role for IL-10 in the innate response to human UTI. The whole bladder transcriptome presented in this work provides new insight into the diversity of innate factors that determine UTI on a genome-wide scale and will be valuable for further data mining. Identification of protective roles for other elements in the transcriptome will provide critical new insight into the complex cascade of events that underpin UTI.en_US
dc.description.peerreviewedYesen_US
dc.description.publicationstatusYesen_US
dc.languageEnglishen_US
dc.language.isoen_US
dc.publisherAmerican Association of Immunologistsen_US
dc.publisher.placeUnited Statesen_US
dc.relation.ispartofstudentpublicationYen_US
dc.relation.ispartofpagefrom781en_US
dc.relation.ispartofpageto792en_US
dc.relation.ispartofissue2en_US
dc.relation.ispartofjournalJournal of Immunologyen_US
dc.relation.ispartofvolume188en_US
dc.rights.retentionYen_US
dc.subject.fieldofresearchMedical Bacteriologyen_US
dc.subject.fieldofresearchcode110801en_US
dc.titleInnate Transcriptional Networks Activated in Bladder in Response to Uropathogenic Escherichia coli Drive Diverse Biological Pathways and Rapid Synthesis of IL-10 for Defense against Bacterial Urinary Tract Infectionen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.facultyGriffith Health, School of Medical Scienceen_US
gro.rights.copyrightSelf-archiving of the author-manuscript version is not yet supported by this journal. Please refer to the journal link for access to the definitive, published version or contact the authors for more information.en_US
gro.date.issued2012
gro.hasfulltextNo Full Text


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