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

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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.