Viral-Bacterial Interactions in the Airway Epithelium

气道上皮中的病毒-细菌相互作用

基本信息

批准号：
7068510
负责人：
RAYMOND J PICKLES
金额：
$ 17.82万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-06-01 至 2008-05-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): It is well known that bacterial infections are often made worse by concurrent viral infections, a condition known as "bacterial superinfection". Infection of the human airways by specific viruses (e.g., influenza, respiratory syncytial virus (RSV) and parainfluenza virus (PIV) have been associated with bacterial pathogens such as non-typified Haemophilus influenzae (NTHi). The airways of cystic fibrosis patients are often colonized by Pseudomonas aeruginosa at similar times that these patients are also susceptible to respiratory viruses although the association between the two pathogen-types is less well documented. Potential mechanisms proposed to result in bacterial super infection include: viral-induced alteration of innate immune systems; reduced mucociliary clearance; the accumulation of excess/altered airway secretions; and, reduced activity of phagocytotic cell-types. Evidence also exists for viral-induced up-regulation of bacterial adherence receptors on epithelial cells. We propose to use an in vitro model of human ciliated airway epithelial cells (HAE) that display many of the physiological functions of the airway epithelium in vivo to perform systematic and quantitative analyses of the effect of viral infection on bacterial superinfection. For these studies we have chosen RSV and PIV3 since we are confident that we can infect HAE with these viruses and maintain the cultures for extended periods post-inoculation. We will attempt to determine the mechanisms that are altered by these viruses that may lead to superinfection by NTHI and PA. We propose the following Specific Aims: 1) Does viral-infection of human ciliated cells promote early bacterial interactions with the airway surface microenvironment? 2) To determine the patho-physiological consequences of viral-infection of ciliated cells that result in bacterial superinfection. 3) To identify potential bacterial attachment factors that are up-regulated by viral-Infection. Elucidation of the processes/molecules that may be altered by viral infection may give insight into new therapeutic targets to limit these effects and thus reduce the pathology associated with bacterial superinfection. The novel aspect of these studies are the bringing together of methods to measure physiological and molecular changes induced by viruses in a single model system that accurately resembles the cell-type distribution of the human airway epithelium.

描述（由申请人提供）：众所周知，通过并发病毒感染，细菌感染通常会变得更糟，这种病被称为“细菌超级感染”。特定病毒（例如，流感，呼吸道综合病毒（RSV）和副氟氟乙烯病毒（PIV）对人类气道的感染与细菌病原体有关易感性的病毒效果较少，导致细菌超级感染的潜在机制包括病毒式免疫系统的变化。在上皮细胞上的粘附受体。为了这些研究我们选择了RSV和PIV3，因为我们有信心可以感染HAE 病毒并维持培养物的长时间接种后。我们将尝试确定这些病毒改变的机制，这些机制可能导致NTHI和PA的近代传播。我们提出以下特定目的：1）人类纤毛细胞的病毒感染是否会促进与气道表面微环境的早期细菌相互作用？ 2）确定纤毛细胞病毒感染的致病生理后果，从而导致细菌性超级感染。 3）确定因病毒感染而上调的潜在细菌依恋因子。阐明可能因病毒感染而改变的过程/分子可能会洞悉新的治疗靶标，以限制这些作用，从而减少与细菌次感染相关的病理学。这些研究的新方面是，在单个模型系统中，病毒诱导的生理和分子变化的方法汇集在一起，该方法准确地类似于人类气道上皮的细胞类型分布。