The Usual Suspects: Chemokines and Microbial Infection of the Central Nervous System

Hickey, Michelle J.; Stiles, Linda N.; Schaumburg, Chris S.

For many years, the central nervous system (CNS) was considered an “immunologically privileged site” — a perspective based on limited immune surveillance when compared to peripheral tissue, muted expression of MHC molecules in the context of an apparent lack of professional antigen presenting cells, and the absence of a classical lymphatic drainage system. Together, these observations supported the notion that the CNS was unable to mount and/or support an immune response. However, over time this view evolved and it is now clear that CNS tissue is neither immunologically inert nor privileged, rather, its immune response is exquisitely sensitive to antigenic challenge. Indeed, overwhelming evidence now indicates that upon microbial infection of the CNS there is often a dynamic and orchestrated localized immune response that culminates with infiltration of antigen-specific lymphocytes, usually resulting in control and elimination of the invading pathogen. It is important to note that not all effective immune responses originating in the CNS are completely beneficial to the host; alternatively, there are instances where immune cell infiltration following infection is associated with severe neuropathology resulting in death or chronic neurodegenerative disease.