Objective

Microglia are tissue resident macrophages within the brain with roles in homeostasis, synaptic pruning and innate immunity. Neuroinflammation has been implicated in the development and progression of several neurodegenerative diseases such as Alzheimer’s and Huntington’s disease¹, with known disease-associated mutations playing a role in microglia function, including TREM2, CD33 and ApoE4^2,3. Induced pluripotent stem cell (iPSC) technology can be used to produce large numbers of microglia and provide a physiologically relevant platform for disease modelling and drug discovery. Using our differentiation method we can produce >10⁹ microglia from iPSC over a period of 2 months culture and have achieved differentiation of over 10 iPSC lines with healthy and disease genotypes. Here we describe the application of iPSC-derived microglia in a series of phagocytosis assays using both flow cytometry and immunocytochemistry for quantification. Using fluorescently labelled S. aureus and beta amyloid (1-42), phagocytosis can be measured and compared between control and disease cell lines, as well as between distinct cell phenotypes. This platform offers a relevant functional assay for modelling disease-associated mutations as well as for applications in drug discovery.