Microglia are a type of glial cell located throughout the brain and spinal cord of the central nervous system (CNS).[1] Microglia account for about 10–15% of cells found within the brain.[2] As the resident macrophage cells, they act as the first and main form of active immune defense in the CNS.[3] Microglia originate in the yolk sac under tightly regulated molecular conditions.[4] These cells (and other neuroglia including astrocytes) are distributed in large non-overlapping regions throughout the CNS.[5][6] Microglia are key cells in overall brain maintenance – they are constantly scavenging the CNS for plaques, damaged or unnecessary neurons and synapses, and infectious agents.[7] Since these processes must be efficient to prevent potentially fatal damage, microglia are extremely sensitive to even small pathological changes in the CNS.[8] This sensitivity is achieved in part by the presence of unique potassium channels that respond to even small changes in extracellular potassium.[7] Recent evidence shows that microglia are also key players in the sustainment of normal brain functions under healthy conditions.[9] Microglia also constantly monitor neuronal functions through direct somatic contacts via their microglial processes, and exert neuroprotective effects when needed.[10][11]
The brain and spinal cord, which make up the CNS, are not usually accessed directly by pathogenic factors in the body's circulation due to a series of endothelial cells known as the blood–brain barrier, or BBB. The BBB prevents most infections from reaching the vulnerable nervous tissue. In the case where infectious agents are directly introduced to the brain or cross the blood–brain barrier, microglial cells must react quickly to decrease inflammation and destroy the infectious agents before they damage the sensitive neural tissue. Due to the lack of antibodies from the rest of the body (few antibodies are small enough to cross the blood–brain barrier), microglia must be able to recognize foreign bodies, swallow them, and act as antigen-presenting cells activating T-cells.