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* Department of Pathology and
Department of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Escherichia coli is the most common pathogen found in urinary tract infections (UTIs), mainly affecting children and women. We report that CD44, a hyaluronic acid (HA) binding protein that mediates cell-cell and cell-matrix interactions, facilitates the interaction of E. coli with urothelial cells and thus the infection of the host. We found that CD44 is constitutively expressed on urothelial cells and that HA accumulates in E. coli-induced UTI. In CD44-deficient mice, the bacterial outgrowth was dramatically less compared with wild-type mice despite similar granulocyte influx in the bladder and in the kidney as well as comparable cytokines/chemokines levels in both genotypes. E. coli was able to bind HA, which adhered to CD44-positive tubular epithelial cells. Most importantly, the interaction of CD44 on tubular epithelial cells with HA facilitated the migration of E. coli through the epithelial monolayer. The results provide evidence that CD44 on urothelial cells facilitates E. coli UTI. Disruption of the interaction between CD44 and HA in the bladder may provide a new approach to prevent and to treat UTI.
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 This work was supported by Grants 907-00-004 and 015-001-061 from the Netherlands Organisation for Scientific Research and Grant PC 125 from the Dutch Kidney Foundation.
2 Address correspondence and reprint requests to Dr. Kasper Rouschop, Department of Pathology, Academic Medical Center, room M2-108, P.O. Box 22660, 1100 DD, Amsterdam, The Netherlands. E-mail address: Kasper.Rouschop{at}maastro.unimaas.nl or reprint requests to Dr. Sandrine Florquin, Department of Pathology, Academic Medical Center, Room M2-108, P.O. Box 22660, 1100 DD, Amsterdam, The Netherlands. E-mail address: S.Florquin{at}amc.uva.nl
3 Abbreviations used in this paper: UTI, urinary tract infection; HA, hyaluronic acid; TEC, tubular epithelial cell; MPO, myeloperoxidase; eGFP, enhanced GFP.
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