Urothelial CD44 facilitates Escherichia coli infection of the murine urinary tract
Urothelial CD44 facilitates Escherichia coli infection of the murine urinary tract
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DOI：
10.4049/jimmunol.177.10.7225
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发表时间：
2006-11-15
影响因子：
4.4
通讯作者：
Florquin, Sandrine
中科院分区：
文献类型：
--
作者：
Rouschop, Kasper M. A.;Sylva, Marc;Florquin, Sandrine
大肠杆菌是泌尿道感染（UTIs）中最常见的病原体，主要影响儿童和妇女。我们报道了透明质酸结合蛋白CD 44介导细胞-细胞和细胞-基质相互作用，促进E.大肠杆菌与尿路上皮细胞接触，从而感染宿主。我们发现CD 44在尿路上皮细胞上组成性表达，HA在E.大肠杆菌诱导的UTI。在CD 44缺陷型小鼠中，尽管膀胱和肾脏中的粒细胞流入相似，两种基因型中的细胞因子/趋化因子水平相当，但与野生型小鼠相比，细菌生长明显减少。E.大肠杆菌能够结合HA，HA粘附在CD 44阳性的肾小管上皮细胞上。最重要的是，肾小管上皮细胞上的CD 44与HA的相互作用促进了E.大肠杆菌通过上皮单层。结果表明，尿路上皮细胞上的CD 44促进E. coli UTI。破坏膀胱中CD 44和HA之间的相互作用可能提供预防和治疗UTI的新方法。
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.