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

支气管上皮细胞暴露于炎症刺激会损害其对鼻病毒的先天免疫反应。

• 批准号: nhmrc : 455567
• 负责人: Prof Peter Wark
• 金额: $ 21.74万
• 依托单位: The University of Newcastle
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/exposure-bronchial-epithelial-response-rhinovirus/100408
• 关键词: Exposure; bronchial; epithelial; cells; inflammatory

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.

哮喘和慢性阻塞性肺疾病（COPD）是澳大利亚最常见的呼吸系统疾病，这两种疾病的特征是呼吸道病毒感染引起的急性发作。这些急性发作最常见的触发因素是通常无害的普通感冒病毒，鼻病毒。这种易感性的原因仍然知之甚少。我们先前已经证明，哮喘患者气道内的细胞更容易受到鼻病毒感染，并且无法有效地对这种感染做出反应。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受试者中。我们将检查哮喘和COPD受试者的气道细胞，并寻找免疫反应缺陷的证据，将其与持续性细菌感染的存在联系起来。然后，我们将培养这些细胞并用鼻病毒感染它们，仔细检查这种对感染的反应受损背后的机制，然后看看我们是否可以通过长期暴露于感染和炎症刺激物来诱导这些细胞的这种损伤。我们的实验室在调查炎症性气道疾病和病毒感染患者方面有着良好的记录，能够获得足够的表征良好的临床样本，并证明了研究病毒上皮细胞相互作用的能力。这项工作将突出那些有风险的发展频繁衰弱加重沿着的原因，这和确定领域的目标新的治疗干预措施。