There is compelling evidence that alternatively activated macrophages are not only a vital homeostatic element in the periphery, but that microglia, and perhaps all tissue specific macrophages, also have the capacity for multiple activation states, defined by the environmental milieu in normal and disease conditions. Although considerably more work pertaining to peripheral macrophages has been accomplished, a significant effort has been made to better define microglial activation phenotypes. The notion that there are either ‘good’ or ‘bad’ activation states of microglia has lost favor. Rather, there exists a spectrum that spans several different activation types with different functions, as represented in our working model (Figure 1). By understanding the nature of microglial activation states and identifying particular induction signals for select states, we come closer to utilizing such signals as therapeutic tools in pathological conditions where detrimental polarization may contribute to disease.
