Immune Sensors, Regulators, and Effectors of Brain Health

Traditionally, the brain was considered an immune-privileged organ. It is now well known that molecular and cellular mechanisms, classically described in the immune system, also occur in the brain. The brain mounts a robust and well-orchestrated innate immune response during infections, injuries, and neurodegenerative diseases. Resident cells of the brain play key roles in this process. Although peripheral immune cells are present at the meningeal borders of the brain, a relatively small number of immune cells infiltrate the parenchyma under physiological conditions. However, if the blood–brain barrier is perturbed in pathological conditions, immune cells infiltrate the brain in large numbers and participate in the immune reaction. Pattern recognition receptors (PRRs) and inflammasomes, sensors of danger signals, are expressed in glia and neurons and mediate the innate immunity of the brain, leading to neuroinflammation, which can be degenerative, protective, or reparative depending on the context. This chapter highlights the role of PRRs, especially toll-like receptors and inflammasomes, in the innate immune response of the brain and neuroinflammation. The danger signals that initiate the immune reaction, the effectors that mediate neuroinflammation, and the underlying mechanisms are discussed in the context of Alzheimer’s and Parkinson’s diseases and brain injuries (BIs).