URINARY TRACT INFECTIONS--IMMUNE BASIS OF SUSCEPTIBILITY

尿路感染——易感性的免疫基础

• 批准号: 3245940
• 负责人: WALTER J HOPKINS
• 金额: $ 17.08万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-05-01 至 1995-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3245940
• 关键词: B lymphocyte; Escherichia coli; SDS polyacrylamide gel electrophoresis; T lymphocyte; antibacterial antibody; bacterial antigens; bactericidal immunity; cellular immunity; enzyme linked immunosorbent assay; female; genetic strain; human subject; immunization; immunopathology; laboratory mouse; phagocytosis; relapse /recurrence; serotyping; urinalysis; urinary bladder epithelium; urinary tract infection; vagina; virulence; western blottings

Urinary tract infections (UTI) remain a common and serious clinical problem that affect 10-20% of all women in their lifetime. Women seeking treatment for acute UTI account for over 5 million visits to physicians' offices annually in the United States Health Care costs to treat only uncomplicated lower tract infections are nearly one billion dollars per year. The most-accepted hypothesis for the pathophysiology of ascending UTI in susceptible women is that uropathogens carried in the fecal flora sequentially colonize the vaginal introitus, urethra, bladder, and finally the kidneys. E. coli strains are responsible for the majority of UTIs and have specific virulence factors such as adhesions for uroepithelial cell receptors, certain O and K antigens, and hemolysins. The reasons for increased susceptibility of female children and certain adult women are unknown but may be due to increased binding of E. coli to epithelial cells lining the vagina and bladder in conjunction with decreased levels of urinary antibody to infecting organisms. There is also an increased incidence of UTIs in immunosuppressed patients (post-transplant and AIDS). The roles of immune defects in UTI have not been seriously studied. Immunodeficiencies in UTI may be a critical and heretofore undefined factor in explaining susceptibilities. Our work with animal models of ascending E. coli UTI in humans has demonstrated that: 1) severe T and B cell immune deficiency increases susceptibility to induced UTI in mice; 2) immune reconstitution of T and B cell-deficient mice restores resistance to UTI; 3) immunization of monkeys or mice with killed, whole-cell vaccines lessens the severity of an induced UTI. This research proposes to document our hypothesis that congenital or induced immunodeficiencies are an important predisposing factor in recurrent E. coli UTI. We will: 1) identify congenital immune deficits in mice that increase susceptibility to UTI; 2) identify immunogenetic predispositions that enhance patients' susceptibility to recurrent UTI; and 3) determine whether E. coli virulence factors modulate the pathogenesis of UTI in immunodeficient mice.

尿路感染（UTI）仍然是一个常见且严重的临床问题 这会影响所有女性一生中的10-20％。 寻求治疗的妇女 对于急性UTI，访问医师办公室的访问量超过500万 每年在美国的医疗保健费用 较低的道感染每年近十亿美元。 关于上升UTI的病理生理学的假设最高的假设 易感性的女性是粪便中携带的尿道病 依次将阴道介绍性，尿道，膀胱定居 肾脏。 大肠杆菌菌株负责大多数UTI和 具有特定的毒力因子，例如乌鲁皮细胞的粘附 受体，某些O和K抗原和血素蛋白。 原因 女童和某些成年女性的敏感性增加是 未知，但可能是由于大肠杆菌与上皮细胞的结合增加所致 与水平降低的阴道和膀胱衬里 感染生物体的尿抗体。 也有增加 免疫抑制患者（移植后和艾滋病）中UTI的发病率。 尚未认真研究免疫缺陷在UTI中的作用。 UTI中的免疫缺陷可能是关键的，迄今为止未定义的因素 在解释敏感性中。 我们与人类上升大肠杆菌UTI的动物模型的合作 证明：1）严重的T和B细胞免疫缺陷增加 小鼠诱发UTI的敏感性； 2）T和B的免疫重建 细胞缺陷小鼠恢复对UTI的抗性； 3）猴子的免疫 或杀死的小鼠，全细胞疫苗减少了诱导的严重程度 UTI。 这项研究建议记录我们的假设，即先天性或 诱导的免疫缺陷是重要的诱发因素 经常性的大肠杆菌UTI。 我们将：1）确定先天性免疫缺陷 增加对UTI敏感的小鼠； 2）识别免疫原性 增强患者复发性UTI敏感性的易感性；和 3）确定大肠杆菌毒力因子是否调节 免疫缺陷小鼠中的尿路感。