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 hormone called GM-CSF activates antifungal defenses to protect against fungal infection. One molecule that controls GM-CSF, called CARD9, appears to be highly important, because humans that have mutations that interfere with the function of CARD9 spontaneously develop life-threatening invasive fungal infections, including of the brain. Although the roles of GM-CSF and of CARD9 in protecting against fungal infections are therefore clear, HOW they protect specific organs is not understood. We believe that these molecules do so by preventing fungus in the gut from escaping into the body. When GM-CSF or CARD9 are malfunctioning, we hypothesize that macrophages in the gut are defective, which allows the fungi normally residing in the gut to escape from the gut tissue and then into specific circulating cells (called monocytes), that then carry the hidden fungus to specific organs, like the brain, leading to life threatening disease. My research aims to understand how GM-CSF and CARD9 enable 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, in whole mice and in cells. 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.