Cholesterol and Hydroxycholesterol Shaping Phagocytosis

现在的报告显示，膜胆固醇和25-羟基胆固醇（25 HC）是免疫细胞通过吞噬作用摄取和杀死病原体所必需的。该项目将测量巨噬细胞中具有遗传或非遗传性胆固醇和25 HC的吞噬作用，以比较和量化不同细菌，真菌和颗粒的摄入。该项目还将根据初步数据显示交错小鼠模型中存在此类缺陷，探讨胆固醇合成、胆固醇在脂质体中的储存及其用于吞噬作用之间的联系。值得注意的是，胆固醇失调现在是社会中的一种普遍状况，我们的研究结果将在基本的分子水平上揭示这可能如何损害免疫防御。

Reports now show that membrane cholesterol and 25-hydroxycholesterol (25HC) are required for immune cells to ingest and kill pathogens by phagocytosis. This project 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. This project 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.