Hannan Thomas J, Hunstad David A
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
Department of Pediatrics, Washington University School of Medicine, 660 S. Euclid Avenue, Campus, 8208, St. Louis, MO, 63110, USA.
Methods Mol Biol. 2016;1333:159-75. doi: 10.1007/978-1-4939-2854-5_14.
Urinary tract infections (UTI) are among the most common bacterial infections of humans. The mouse provides an excellent and tractable model system for cystitis and pyelonephritis caused by Escherichia coli and other uropathogens. Using a well-established model of experimental cystitis in which the bladders of female mice are infected via transurethral catheterization, the molecular details of the pathogenesis of bacterial cystitis have been substantially illuminated in the last decade. Uropathogenic E. coli attach to bladder epithelium (both in human and mouse) via adhesive type 1 pili, establish a replicative niche within epithelial cell cytoplasm, and form intracellular bacterial communities that are protected from antibiotic effects and immune clearance. The use of different inbred and mutant mouse strains offers the opportunity to study outcomes of infection, including resolution, formation of quiescent intracellular bacterial reservoirs, chronic bacterial cystitis, and recurrent infections. Urine, bladder, and kidney tissues can be analyzed by bacterial culture, histology, immunohistochemistry, immunofluorescent and confocal microscopy, electron microscopy, and flow cytometry, while a broad array of soluble markers (e.g., cytokines) can also be profiled in serum, urine, and tissue homogenates by ELISA, Western blotting, multiplex bead array, and other approaches. This model promises to afford continued opportunity for discovery of pathogenic mechanisms and evaluation of therapeutic and preventive strategies for acute, chronic, and recurrent UTI.
尿路感染（UTI）是人类最常见的细菌感染之一。小鼠为大肠杆菌和其他尿路致病菌引起的膀胱炎和肾盂肾炎提供了一个出色且易于处理的模型系统。利用一种成熟的实验性膀胱炎模型，通过经尿道插管感染雌性小鼠的膀胱，在过去十年中，细菌性膀胱炎发病机制的分子细节已得到充分阐明。尿路致病性大肠杆菌通过1型菌毛附着于膀胱上皮（在人类和小鼠中均如此），在上皮细胞质内建立一个复制龛，并形成细胞内细菌群落，这些群落可免受抗生素作用和免疫清除。使用不同的近交系和突变小鼠品系提供了研究感染结果的机会，包括感染的消退、静止细胞内细菌储存库的形成、慢性细菌性膀胱炎和复发性感染。尿液、膀胱和肾脏组织可通过细菌培养、组织学、免疫组织化学、免疫荧光和共聚焦显微镜、电子显微镜以及流式细胞术进行分析，而一系列可溶性标志物（如细胞因子）也可通过ELISA、蛋白质印迹、多重微珠阵列和其他方法在血清、尿液和组织匀浆中进行分析。该模型有望为发现致病机制以及评估急性、慢性和复发性UTI的治疗和预防策略提供持续的机会。
