Monocytes are the primary cells mediating the innate immune response. They are found in all tissues, including the brain. Monocytes in the brain, which also are referred to as microglia, fall into two main categories: proinflammatory M1 monocytes/microglia and trophic M2 monocytes/microglia. M1 monocytes/microglia participate in the acute proinflammatory responses of the innate immune system; in addition, they also convey signals to the adaptive immune cells (i.e., T and B cells) through the MHC molecules they carry on their cell surface. These signals help create a persistent sensitization to pathogens (e.g., in the form of antibodies that mediate immunization). These proinflammatory effects occur in response to pathogens as well as tissue damage, cell death, and degeneration. Thus, M1 microglia and other monocyte-like cells consistently express multiple cytokine receptors and TLRs that, when activated, induce innate immune genes, such as proinflammatory cytokines, proteases, and oxidases, which help to break down, process, and remove damaged cells and tissue. In contrast, the M2 monocytes/microglia mediate a delayed response that initiates wound-healing trophic signaling and seem to be critical for healing. Both monocytes in
