We also demonstrate the use of iMGLs to investigate human microglial function as a therapeutic target in human disease. A recent study implicated complement and increased microglia-mediated pruning of synapses early in AD (Hong et al., 2016a; Hong et al., 2016b). Here, we found that blocking CR3, via anti-CD11b, in iMGLs reduces phagocytosis of human synaptosomes. Our findings provide one of the first examples, to our knowledge, of quantitative evidence showing human microglia engulfing human synaptosomes predominately via the CR3 axis, as implicated by transgenic mouse studies (Hong et al., 2016a). Moreover, we highlight the utility of iMGLs to examine microglia-targeted AD therapies, such as anti-CD11b, in phagocytic assays and to potentially examine or validate other complement-targeted therapies in development.
