This detailed classification of M2 cells has been primarily carried out in the periphery. Whether or not this will extend to brain resident microglia is yet to be seen. However, some investigators have taken to using the M2a-c nomenclature to discuss populations of alternatively activated microglia [54]. This poses potential problems, as certain M2 markers do not appear to be expressed in the CNS (Table 1). The best example of this is the first observed alternative macrophage marker, CD206, which is only seen in perivascular or choroid-plexus-associated macrophages and not expressed by parenchymal microglia [55]. Furthermore, microglia are not macrophages that migrate into the brain, but instead are known to represent a distinct population of resident tissue mesenchymal cells that populate the CNS during early development [56,57]. Importantly, because the origins and responses of microglia and macrophages are different, the roles they play in mitigating or propagating pathology could be different as well.
