Exposure of bronchial epithelial cells to inflammatory stimuli impairs their innate immune response to rhinovirus.

哮喘和慢性阻塞性肺病（COPD）是澳大利亚最常见的呼吸系统疾病，这两种疾病的特点都是由呼吸道病毒感染引起的急性发作。这些急性发作最常见的诱因是通常无害的普通感冒病毒，鼻病毒。人们对这种易感性的原因仍然知之甚少。我们之前的研究表明，哮喘患者呼吸道的细胞更容易受到鼻病毒的感染，并且不能对这种感染做出有效的反应。我们建议进一步阐明这一缺陷，并首次确定它是否也存在于COPD患者中。我们将检查哮喘和慢性阻塞性肺病患者的气道细胞，寻找免疫反应缺陷的证据，并将其与持续细菌感染的存在联系起来。然后我们将培养这些细胞，用鼻病毒感染它们，仔细检查这种对感染的受损反应背后的机制，然后看看我们是否可以在这些细胞中长期暴露于感染和炎症刺激下诱导这种损伤。我们的实验室在研究炎症性呼吸道疾病和病毒感染患者方面有着良好的记录，拥有无与伦比的充足的临床样本，并且已经证明了研究病毒上皮细胞相互作用的能力，因此可以很好地研究这些问题。这项工作将突出那些有发展频繁的衰弱性恶化的风险以及其原因，并确定针对新的治疗干预措施的领域。

Asthma and chronic obstructive pulmonary disease (COPD) are the most common respiratory conditions in Australia, both of these conditions are characterised by acute attacks precipitated by respiratory virus infections. The most common trigger for these acute attacks is the usually innocuous common cold virus, rhinovirus. The reason for this susceptibility remains poorly understood. We have previously shown that the cells lining the airways of asthmatics are more susceptible to infection with rhinovirus and fail to react to this infection effectively. We propose to further elucidate this defect and for the first time determine if it is also present in subjects with COPD. We will examine the airway cells of subjects with asthma and COPD and look for evidence of a defective immune response, relating this to the presence of persistent bacterial infection. We will then grow these and infect them with rhinovirus, carefully examining the mechanisms behind this impaired response to infection and then see if we can induce such impairment in these cells with chronic exposure to infection and inflammatory stimuli. Our laboratory is well placed to investigate these problems with an established track record in investigating patients with inflammatory airways disease and virus infection, unparalleled access to sufficient well characterised clinical samples and have demonstrated the ability to study virus epithelial cell interactions. This work will highlight those at risk of developing frequent debilitating exacerbations along with the reasons for this and identify areas to target novel therapeutic interventions.