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

Duell, Benjamin L., Carey, Alison J., Tan, Chee K., Cui, Xiangqin, Webb, Richard I., Totsika, Makrina, Schembri, Mark A., Derrington, Petra, Irving-Rodgers, Helen, Brooks, Andrew J., Cripps, Allan W., Crowley, Michael and Ulett, Glen C. (2012) 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. Journal of Immunology, 188 2: 781-792. doi:10.4049/jimmunol.1101231


Author Duell, Benjamin L.
Carey, Alison J.
Tan, Chee K.
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 C.
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
Formatted 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
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
1550-6606
Publication date 2012-01-15
Year available 2011
Sub-type Article (original research)
DOI 10.4049/jimmunol.1101231
Volume 188
Issue 2
Start page 781
End page 792
Total pages 12
Place of publication Bethesda, MD, United States
Publisher American Association of Immunologists
Collection year 2012
Language eng
Formatted 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online before print December 19, 2011

 
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Created: Thu, 09 Feb 2012, 09:52:56 EST by Lucy O'Brien on behalf of School of Chemistry & Molecular Biosciences