Cholesterol and Hydroxycholesterol Shaping Phagocytosis (2014-2016)

Reports now show that membrane cholesterol and 25-hydroxycholesterol (25HC) are required for immune cells to ingest and kill pathogens by phagocytosis. We will measure phagocytosis in macrophages with genetically or pharmacologically varied cholesterol and 25HC, to compare and quantify the ingestion of different bacteria, fungi and particles. We will also address the link between cholesterol synthesis, its storage in lipid bodies and its availability for phagocytosis, based on preliminary data showing such defects in the staggerer mouse model. Notably, cholesterol dysregulation is now a prevalent condition in society and our results will reveal at a fundamental, molecular level how this might compromise immune defenses.