Immunology of Central Nervous System Pathogens

A surprisingly large number of bacteria, fungi, helminthes, parasites, and viruses invade the central nervous system (CNS) as a feature of their typical pathophysiology in humans. This process involves multiple steps and culminates in crossing the blood-brain or blood-cerebrospinal fluid barriers from the bloodstream, or by invading along nerve routes, for example, olfactory, trigeminal, or even peripheral neurons. Each point leading to CNS infection is a complex interplay between pathogens and innate and adaptive host defenses. Microbial factors evolved to avoid, subvert, or overcome them. In addition, deficiencies in host defenses due to underlying genetic or acquired conditions, for example, HIV/AIDS, as well as comorbid metabolic conditions also influence an individual's susceptibility to CNS infection. The host's response is similarly shaped by multiple factors. These include the prevailing immune suppressive environment of the brain at steady state, the route and magnitude of microbial invasion, the sensing molecules used to detect microbial invasion, and the downstream inflammatory cascades that are triggered.