Microglia as liaisons between the immune and central nervous systems: functional implications for multiple sclerosis

Abstract

Multiple sclerosis is a chronic demyelinating inflammatory disease of the central nervous system (CNS). As the tissue macrophage of the CNS, microglia have the potential to regulate and be regulated by cells of the CNS and by CNS-infiltrating immune cells. The exquisite sensitivity of microglia to these signals, coupled with their ability to develop a broad range of effector functions, allows the CNS to tailor microglial function for specific physiological needs. However, the great plasticity of microglial responses can also predispose these cells to amplify disproportionately the irrelevant or dysfunctional signals provided by either the CNS or immune systems. The consequences of such an event could be the conversion of self-limiting inflammatory responses into chronic neurodegeneration and may explain in part the heterogeneous nature of multiple sclerosis.

Fig. 1

Knowing when to stop. Microglia are capable of developing a broad range of effector functions, determined in part by environmental signals from neurons, glia, and CNS-infiltrating immune cells and in part to their prior activation/developmental state. Their great plasticity and sensitivity to external cues allow for fine control of microglial effector function but also predispose microglia to develop maladaptive functions in response to dysregulated environmental signals. APC, antigen-presenting cell.