Grant: Project Grant

Invasive fungal infections affect more than 2 million people worldwide annually, and result in death for more than half of these patients. In a healthy immune system, a molecule called CARD9 activates antifungal immune responses and this protects against infection. We know this because mutations that disrupt the function of CARD9 are associated with life-threatening fungal infections of the brain. Although the critical role of CARD9 in promoting antifungal immunity is therefore clear, how CARD9 protects specific organs is not understood. We believe that this happens because defective CARD9 allows the normal fungal community in the gut to escape into specific circulating cells (called monocytes), which then enter the brain (to become macrophages that, in this case, are dysfunctional) leading to life-threatening disease. My research aims to understand how CARD9 enables monocytes and macrophages to combat fungal infections at the level of the gut, blood and brain. I will use innovative cutting-edge techniques to investigate these processes. This exciting research will provide important and new insights into organ- and cell-specific immunity to fungal infections, opening the door to developing new ways to treat these devastating infections.