URINARY TRACT INFECTIONS--IMMUNE BASIS OF SUSCEPTIBILITY

描述（改编自申请人摘要）：尿路 感染（UTI），估计发生在高达50%的所有妇女在其 一生 每年约有700万妇女患急性 据估计， 成本 复发性感染发生在10-15%的成年女性中， 正在进行的医疗护理和使用抗生素， 预防性地。 此外，下尿路感染可以上升到 肾，可能导致肾损伤或菌血症。 宿主抗性 泌尿道感染是由几种不同的机制，包括先天性 免疫、炎症反应和适应性免疫反应。 细胞因子， 吞噬细胞、自然杀伤细胞和T细胞在宿主防御中是活跃的， 感染. 我们的初步结果表明，功能缺陷 在这些成分中的任何一种都会导致感染的严重程度增加， 实验动物的膀胱和肾脏。 也有证据表明 先天和早期细胞防御可以防止膀胱感染 上升到肾脏 初步的基因研究表明 宿主对尿路感染的易感性增加有遗传因素。 因此，总体目标是更明确地界定东道方 在UTI期间活跃的反应，并确定遗传因素， 增加敏感性。 具体目标是：（1）确定 在UTI期间活跃的细胞宿主防御机制， 特别是那些对预防下尿路感染最重要的药物， 从上行到肾脏的感染; 2）评估假设， 抗体介导的对E.大肠杆菌抗原 女性与T细胞调节或诱导抗体有关 反应; 3）评估遗传性状增加的假设 部分妇女复发性尿路感染易感性家族史分析 遗传模式; 4）评估遗传位点（或 位点）会增加对诱导性尿路感染的易感性。

DESCRIPTION (Adapted from the Applicant's Abstract): Urinary tract infections (UTI) are estimated to occur in up to 50% of all women in their lifetimes. Approximately seven million women per year develop acute infections that account for an estimated one billion dollars in health care costs. Recurrent infections develop in 10-15% of adult women and require ongoing medical care and use of antibiotics both acutely and prophylactically. In addition, lower tract infections can ascend to the kidneys, possibly leading to kidney damage or bacteremia. Host resistance to UTI's is comprised of several different mechanisms that include innate immunity, inflammatory responses, and adaptive immune responses. Cytokines, phagocytes, natural killer cells, and T cells are active in host defense to infections. Our preliminary results have shown that functional deficiencies in any of these components leads to increased severity of infections in the bladder and kidneys of experimental animals. There is also evidence that innate and early cellular defenses can act to prevent bladder infections from ascending to the kidneys. Preliminary genetic studies have indicated that increased host susceptibility to UTI's has a heritable component. Therefore, the overall objective is to more clearly define the host responses that are active during a UTI and to identify genetic factors that increase susceptibility. The specific aims are: 1) to identify the role of cellular host defense mechanisms that are active during a UTI and, in particular those that are most important in preventing lower tract infections from ascending to the kidneys; 2) to evaluate the hypothesis that antibody-mediated hyporesponsiveness to E. coli antigens in UTI-susceptible women is associated with T cell regulation or induction of antibody responses; 3) to evaluate the hypothesis that a heritable trait increases the susceptibility to some women to recurrent UTIs by analysis of familial inheritance patterns; 4) to evaluate the hypothesis that a genetic locus (or loci) in mice will increase susceptibilityto an induced UTI.