KILLING OF MYCOBACTERIUM TUBERCULOSIS IN MACROPHAGES VIA THE P2X7 RECEPTOR

通过 P2X7 受体杀死巨噬细胞中的结核分枝杆菌

• 批准号: nhmrc : 211112
• 负责人: Dr Bernadette Saunders
• 金额: $ 15.09万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2002
• 资助国家: 澳大利亚
• 起止时间: 2002-01-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/killing-mycobacterium-tuberculosis-p2x7-receptor/96596
• 关键词: KILLING; MYCOBACTERIUM; TUBERCULOSIS; MACROPHAGES; VIA

Tuberculosis remains an enormous global health problem. Some 32% of the world population are infected, with over 1 million persons dying each year. The risk of an infected individual developing clinical disease ranges from 2-23% for their lifetime. We know that both environmental factors, such as declining socio-economic conditions, and genetic risk factors such as HLA type contribute to the likelihood of an individual developing disease, but current known factors are insufficient to fully account for the risk attributed to genetics. The aim of this project is to investigate another potential risk factor involved in the development of tuberculosis, that of P2X7 receptor function. A natural compound, ATP, when added to macrophages is able to kill tuberculosis organisms residing within the macrophage. This process occurs when ATP activates the P2X7 receptor. We have recently identified a mutation in the P2X7 receptor, which causes a loss of receptor function. Individuals who have this mutation are unable to respond to ATP and hence may be unable to kill tuberculosis. Our studies will determine if the mutation we have identified in the P2X7 receptor prevents or inhibits ATP mediated killing of mycobacteria. Furthermore we will determine the frequency of this mutation in TB patients and the general population to determine if this mutation in the P2X7 receptor is a risk factor for the development of tuberculosis disease.

结核病仍然是一个巨大的全球健康问题。全世界约32%的人口受到感染，每年有100多万人死亡。受感染个体一生中发生临床疾病的风险为2-23%。我们知道，环境因素（如社会经济条件下降）和遗传风险因素（如HLA类型）都有助于个体发生疾病的可能性，但目前已知的因素不足以完全解释遗传因素造成的风险。该项目的目的是研究与结核病发展有关的另一个潜在风险因素，即P2 X7受体功能。一种天然化合物，ATP，当加入到巨噬细胞中时，能够杀死巨噬细胞内的结核菌。这个过程发生在ATP激活P2 X7受体时。我们最近发现了P2 X7受体的突变，导致受体功能丧失。具有这种突变的个体无法对ATP作出反应，因此可能无法杀死结核病。我们的研究将确定我们在P2 X7受体中鉴定的突变是否阻止或抑制ATP介导的对分枝杆菌的杀伤。此外，我们将确定这种突变在结核病患者和一般人群中的频率，以确定P2 X7受体中的这种突变是否是结核病发展的危险因素。