Journal article
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
The Journal of immunology (1950), v 188(2), pp 781-792
15 Jan 2012
PMID: 22184725
Featured in Collection : UN Sustainable Development Goals @ Drexel
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 systems-level 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. The Journal of Immunology, 2012, 188: 781-792.
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Details
- 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
- Creators
- Benjamin L. Duell - Griffith UniversityAlison J. Carey - Griffith UniversityChee K. Tan - Griffith UniversityXiangqin Cui - University of Alabama at BirminghamRichard I. Webb - The University of QueenslandMakrina Totsika - The University of QueenslandMark A. Schembri - The University of QueenslandPetra Derrington - Gold Coast HospitalHelen Irving-Rodgers - The University of AdelaideAndrew J. Brooks - The University of QueenslandAllan W. Cripps - Griffith UniversityMichael Crowley - University of Alabama at BirminghamGlen C. Ulett - Griffith University
- Publication Details
- The Journal of immunology (1950), v 188(2), pp 781-792
- Publisher
- American Association of Immunologists
- Number of pages
- 12
- Grant note
- Griffith University Gold Coast Hospital 569674 / National Health and Medical Research Council; National Health and Medical Research Council (NHMRC) of Australia
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics; College of Medicine; Drexel University
- Web of Science ID
- WOS:000299323700032
- Scopus ID
- 2-s2.0-84855989754
- Other Identifier
- 991020100203104721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology