Different inflammatory responses are associated with Ureaplasma parvum-induced UTI and urolith formation.
Different inflammatory responses are associated with Ureaplasma parvum-induced UTI and urolith formation.
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DOI：
10.1186/1471-2334-9-9
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发表时间：
2009-01-26
影响因子：
3.7
通讯作者：
Brown MB
中科院分区：
文献类型：
--
作者：
Reyes L;Reinhard M;Brown MB
流行病学研究表明，脲原体与人类泌尿生殖道疾病之间存在密切联系。由于健康人可以被脲原体定殖，其作为病原体的作用仍然存在争议。为了开始确定宿主在疾病中的作用，我们使用Fischer 344（F344）大鼠建立了泌尿道感染（UTI）的啮齿动物模型。用无菌肉汤、101、103、105、107或109 log CFU的大鼠适应性微小脲原体菌株接种动物。感染的动物表现出两种不同的配置文件，无症状的UTI和UTI并发鸟粪石尿石症。U.小孢子虫对UTI的发病率有影响，接种≥ 107 CFU的动物占50%~ 57%。小孢子仍有感染（P < 0.04）。但接种量对免疫应答无影响。小的无症状性UTI的特征是最小免疫应答，主要是单核细胞和淋巴细胞，病变有限，尿IFN-γ、IL-18和MCP-1水平升高（P ≤ 0.02）。UTI合并鸟粪石形成的特征是免疫反应增强，主要是嗜酸性（P ≤ 0.0001），病变显示广泛的尿路上皮增生（P ≤ 0.0001），尿液中IL-1α、IL-1β和GRO/KC占优势（P ≤ 0.02）。无症状UTI动物的肾脏感染率也显著较高（P ≤ 0.0005）。与U.细小脲原体感染主要取决于宿主特异性因素，而不是脲原体微生物负荷。F344大鼠的免疫应答与人的脲原体相关疾病相似。因此，该感染模型是阐明U.微小的宿主相互作用，赋予UTI和疾病。
Epidemiologic studies show a strong association between Ureaplasmas and urogenital tract disease in humans. Since healthy humans can be colonized with Ureaplasmas, its role as a pathogen remains controversial. In order to begin to define the role of the host in disease, we developed a rodent model of urinary tract infection (UTI) using Fischer 344 (F344) rats. Animals were inoculated with sterile broth, 101, 103, 105, 107, or 109 log CFU of a rat-adapted strain of Ureaplasma parvum. Infected animals exhibited two distinct profiles, asymptomatic UTI and UTI complicated with struvite urolithiasis. Inoculum dose of U. parvum affected the incidence of UTI, and 50% to 57% of animals inoculated with ≥ 107 CFU of U. parvum remained infected (p < 0.04). However, inoculum dose did not influence immune response to U. parvum. Asymptomatic UTI was characterized by a minimal immune response that was predominantly monocytic and lymphocytic, with limited lesions, and elevated urinary levels of IFN-γ, IL-18 and MCP-1 (P ≤ 0.02). UTI complicated with struvite formation was characterized by an exaggerated immune response that was mostly neutrophilic (P ≤ 0.0001), with lesions that showed extensive uroepithelial hyperplasia (P ≤ 0.0001), and a predominance of IL-1α, IL-1β, and GRO/KC in the urine (P ≤ 0.02). Animals with asymptomatic UTI also had a significantly high rate of kidney infection (P ≤ 0.0005). Complications associated with U. parvum infection are primarily dependent upon host-specific factors rather than Ureaplasma microbial load. The immune response in F344 rats is similar to that which occurs in humans with ureaplasmal associated disease. Therefore, this model of infection is a useful tool for elucidating U. parvum-host interactions that confer UTI and disease.