Innate 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 Infection

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Title Innate 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 Infection
Author Duell, Ben; Carey, Alison; Tan, CK; Cui, Xiangqin; Webb, Richard I.; Totsika, Makrina; Schembri, Mark A.; Derrington, Petra; Irving-Rodgers, Helen; Brooks, Andrew J.; Cripps, Allan W; Crowley, Michael; Ulett, Glen Charles
Journal Name Journal of Immunology
Year Published 2012
Place of publication United States
Publisher American Association of Immunologists
Abstract Early 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.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.4049/jimmunol.1101231
Copyright Statement Self-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.
Volume 188
Issue Number 2
Page from 781
Page to 792
ISSN 1550-6606
Date Accessioned 2012-07-09
Date Available 2013-06-05T02:39:30Z
Language en_US
Research Centre Griffith Health Institute; Molecular Basis of Disease
Faculty Griffith Health Faculty
Subject Medical Bacteriology
URI http://hdl.handle.net/10072/47640
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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