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CUTTING EDGE |
* Institute for Systems Biology, Seattle, WA 98103; Department of
Immunology,
Department of Medicine, and
Department of Pathology, University of Washington School of Medicine, Seattle, WA 98195; and
¶ Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
Although TLR5 regulates the innate immune response to bacterial flagellin, it is unclear whether its function is essential during in vivo murine infections. To examine this question, we challenged Tlr5–/– mice transurethrally with Escherichia coli. At 2 days postinfection, wild-type mice exhibited increased inflammation of the bladder in comparison to Tlr5–/– mice. By day 5 postinfection, Tlr5–/– mice had significantly more bacteria in the bladders and kidneys in comparison to wild-type mice and showed increased inflammation in both organs. In addition, flagellin induced high levels of cytokine and chemokine expression in the bladder that was dependent on TLR5. Together, these data represent the first evidence that TLR5 regulates the innate immune response in the urinary tract and is essential for an effective murine in vivo immune response to an extracellular pathogen.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 T.R.H. was supported by National Institutes of Health Grant R01 AI061464-02, K.D.S. was supported by National Institutes of Health Grant R01 AI062859, and A.A. was supported by National Institutes of Health Grant R01 AI052286.
2 E.A.-N. and T.R.H. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Alan Aderem, Institute for Systems Biology, 1441 North 34th Street, Seattle, WA 98103. E-mail address: aderem{at}systemsbiology.org
4 Abbreviations used in this paper: UPEC, uropathogenic E. coli; UTI, urinary tract infection; EF1
, elongation factor 1; CHO, Chinese hamster ovary; LB, Luria-Bertani; IQR, interquartile range; WT, wild type.
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