MODELING AIRWAY RESPONSE TO BORDETELLA SP INFECTION

描述（申请人摘要）：尽管疫苗接种在2005年后期引入， 20世纪40年代， 尽管如此，这种疾病仍然是地方性的，影响了6000多万人， 每年。在美国，报道的波氏杆菌病的发病率是 低，每年确诊病例2,000 - 6,000例。然而，这个数字是一个 由于诊断的困难而被低估，博德特氏菌病 免疫功能低下和成年人群中的发病率稳步上升， 70年代末本研究旨在了解波氏杆菌 衍生因素及其对启动和进展的影响 气道细胞发病机制细菌性病原体与其 主持人的范围可以从建立一个共同的关系， 可能致命的疾病在发病过程中，细菌不断监测 它们的环境，并相应地调整毒力基因的表达。是 认为来自博德特氏菌属的病原体表达特定的基因产物， 用于优先结合气道上皮中的纤毛细胞。 此外，它表明，这种结合启动宿主细胞信号传导 途径-包括细胞内Ca 2+浓度的瞬时变化 ([Ca2+]i）-和宿主细胞细胞骨架重排，其有助于建立 有利于博德特氏菌建立和发展的当地环境 sp.感染。本实验采用原代培养的兔气管上皮细胞， 细胞和B.支气管败血症菌株在遗传上锁定了特定的毒力 状态或表达选择性毒力基因将用于模拟细胞 致病性在启动博德特氏菌属感染中的作用。视频显微镜将是 用于分析物理附着的变化，数字成像显微镜， 测定宿主细胞信号传导的变化，免疫细胞化学测定 与特定基因产物相关的宿主细胞细胞骨架， 细胞致病过程中的博德特氏菌。更好地了解 细菌/宿主相互作用及其生理意义 应导致更好地发展预防疗法和治疗 对抗细菌入侵的策略。

DESCRIPTION (Applicant's Abstract): Although vaccination introduced in the late 1940s has been effective in reducing the incidence of Bordetella disease in humans, the disease is still endemic, and affects more than 60 million people annually. In the United States, the reported incidence of Bordetella disease is low, with 2,000 - 6,000 diagnosed cases each year. However, this number is an underestimate due to the difficulty of diagnosis, and Bordetella disease has been steadily increasing in immunocompromised and adult populations since the late 1970s. This research is directed at the understanding of Bordetella derived factors and their impact on the initiation and the progression of airway cell pathogenesis. The interaction between bacterial pathogens and their hosts can range from the establishment of a commensal relationship to a potentially lethal disease. During pathogenesis, bacteria continually monitor their environment and adjust virulence gene expression accordingly. It is thought pathogens from Bordetella sp. express specific gene products that allow for preferential binding of ciliated cells in the airway epithelium. Furthermore, it is suggested that this binding initiates host cell signaling pathways-including transient changes in intracellular Ca2+ concentration ([Ca2+]i)-and host cell cytoskeleton rearrangements that help establish a favorable local environment for the establishment and progression of Bordetella sp. infection. In this proposal, primary cultured rabbit tracheal epithelial cells and B. bronchiseptica strains genetically locked in specific virulence states or expressing selective virulence genes will be used to model cell pathogenesis in initiating Bordetella sp. infection. Video microscopy will be used to assay changes in physical attachment, digital imaging microscopy to assay changes in host cell signaling an immunocytochemistry to assay changes in the host cell cytoskeleton associated with specific gene products produced by Bordetella sp. during cell pathogenesis. A greater understanding of bacterial/host interactions and their resulting physiological significance should lead to better development of prevention therapies and treatment strategies against bacterial invasion.