The presence of multiple activation phenotypes for microglia is a relatively new concept that is only starting to gain momentum. Therefore, the amount of data is still sparse on the roles they play. However, the activation status of peripheral macrophages has been an area of interest ever since Stein and colleagues observed that interleukin 4 (IL-4) induced macrophages to express the mannose receptor [8]. Such a phenotype was previously unseen and was therefore designated ‘alternative’. Since then, multiple laboratories have characterized and classified ‘unique’ activation states, leading to a somewhat convoluted set of nomenclature. However, recent evidence suggests that the in-vitro data originally used to identify macrophage phenotypes does not accurately model the complex tissue environment and the original descriptions are somewhat simplistic [9]. Moreover, unlike the periphery, in which these cells have been studied for more than 20 years, we are just beginning to closely examine these complicated activation states in the CNS. Therefore, a deeper understanding of the heterogeneity and different phenotypes of microglia is needed; assumptions that information gleaned in the periphery will translate to the brain may not be correct.
