Pathogens Driving Central Nervous System Immunopathology

A surprisingly large number of bacteria, fungi, helminths, parasites, and viruses invade the central nervous system (CNS) as a feature of their typical pathophysiology in humans with serious consequences for brain function. 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 that connect the CNS with the periphery. CNS invasion triggers local host defense mechanisms in the CNS as well as recruitment of immune cells from the periphery. Multiple factors including deficiencies in host defenses due to underlying genetic or acquired conditions e.g. HIV/AIDS, and the age of the host influence an individual’s susceptibility to CNS infection and their immune response to it. Additionally, there is a growing awareness that brain inflammation and neurocognitive function are also affected by high-grade systemic infections by pathogens that do not enter the CNS proper. Therefore, infection-related CNS immunopathology should be considered more broadly than only a response restricted to CNS-penetrating pathogens.