Dissecting how the NLRP3 inflammasome provokes blood brain barrier dysfunction during cerebral malaria

剖析 NLRP3 炎症小体如何在脑型疟疾期间引发血脑屏障功能障碍

• 批准号: MR/W028867/1
• 负责人: David Brough
• 金额: $ 71.33万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FW028867%2F1
• 关键词: Dissecting; how; NLRP3; inflammasome; provokes

Diseases caused by parasites have devastating consequences on the human population. The most important disease caused by a parasite is malaria which causes over 400,000 deaths every year. One of the most devastating consequences of malaria is a syndrome called cerebral malaria. Cerebral malaria is where the disease has affected the brain. The outcome of cerebral malaria, which is most prevalent in children, is death, caused by swelling of the brain. This swelling occurs because the barrier between the blood and the brain breaks down. The integrity of this 'blood-brain barrier' is critical for normal brain function and survival. Our research has provided good clues to how the blood-brain barrier breaks down in cerebral malaria. The main culprit are our own immune systems that are activated by the disease and turn against our own bodies. A specific part of our immune system, called the 'NLRP3 inflammasome' becomes active to break the blood-brain barrier. If we can understand how, when, and where this happens we will be better able to develop ways of blocking the NLRP3 inflammasome and its effects. If we can do this then we may be better able to treat cerebral malaria, and ultimately prevent the deaths of hundreds of thousands of children every year. Our research may also be relevant to other diseases where the blood-brain barrier is compromised.

寄生虫引起的疾病对人类人口造成毁灭性的后果。由寄生虫引起的最重要的疾病是疟疾，每年造成40多万人死亡。疟疾最具破坏性的后果之一是一种称为脑型疟疾的综合征。脑型疟疾就是这种疾病影响大脑的地方。脑型疟疾在儿童中最常见，其结果是由脑肿胀引起的死亡。这种肿胀是因为血液和大脑之间的屏障被破坏了。这种“血脑屏障”的完整性对于正常的大脑功能和生存至关重要。我们的研究为脑型疟疾中血脑屏障如何被破坏提供了很好的线索。主要的罪魁祸首是我们自己的免疫系统，这些系统被疾病激活，并对我们自己的身体不利。我们免疫系统的一个特殊部分，称为NLRP3炎症小体，会活跃起来打破血脑屏障。如果我们能够了解这种情况发生的方式、时间和地点，我们将能够更好地开发出阻止NLRP3炎症体及其影响的方法。如果我们能做到这一点，那么我们可能会更好地治疗脑型疟疾，并最终防止每年数十万儿童的死亡。我们的研究也可能与血脑屏障受损的其他疾病相关。