Schilling J D, Mulvey M A, Vincent C D, Lorenz R G, Hultgren S J
Department of Molecular Microbiology, Department of Pathology and Immunology, and Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
J Immunol. 2001 Jan 15;166(2):1148-55. doi: 10.4049/jimmunol.166.2.1148.
One mechanism of initiating innate host defenses against uropathogenic Escherichia coli (UPEC) is the production of cytokines by bladder epithelial cells; however, the means by which these cells recognize bacterial pathogens is poorly understood. Type 1 pili, expressed by the majority of UPEC, have been shown to have a critical role in inducing the expression of IL-6 in bladder epithelial cells after exposure to E. coli. In this study, we demonstrate that type 1 pili are not sufficient to activate IL-6 production by bladder epithelial cells. Instead, it was shown that bacterial invasion mediated by type 1 pili augments bladder epithelial responses to E. coli via an LPS-dependent mechanism, leading to the production of IL-6. RNA transcripts for the LPSR Toll-like receptor 4 (TLR4) was detected in cultured bladder epithelial cells. The in vivo role of TLR4 was assessed using C3H/HeJ mice, which express a dominant negative form of TLR4. After infection with UPEC, C3H/HeJ mice have large foci of intracellular bacteria that persist within the bladder epithelium in the absence of any notable inflammatory response. These results indicate that LPS is required for bacterial invasion to enhance host responses to E. coli within the bladder.
启动宿主针对尿路致病性大肠杆菌（UPEC）的固有防御的一种机制是膀胱上皮细胞产生细胞因子；然而，这些细胞识别细菌病原体的方式却知之甚少。大多数UPEC表达的1型菌毛已被证明在暴露于大肠杆菌后诱导膀胱上皮细胞中IL-6的表达方面起关键作用。在本研究中，我们证明1型菌毛不足以激活膀胱上皮细胞产生IL-6。相反，研究表明，由1型菌毛介导的细菌入侵通过一种依赖脂多糖（LPS）的机制增强膀胱上皮对大肠杆菌的反应，导致IL-6的产生。在培养的膀胱上皮细胞中检测到LPSR Toll样受体4（TLR4）的RNA转录本。使用表达显性负性形式TLR4的C3H/HeJ小鼠评估TLR4在体内的作用。感染UPEC后，C3H/HeJ小鼠有大量细胞内细菌聚集，这些细菌在膀胱上皮内持续存在，且没有任何明显的炎症反应。这些结果表明，细菌入侵需要LPS来增强宿主对膀胱内大肠杆菌的反应。
