Cryptococcus neoformans-astrocyte interactions: effect on fungal blood brain barrier disruption, brain invasion, and meningitis progression.

ABSTRACT

Cryptococcus neoformans is an opportunistic, neurotropic, and encapsulated fungus that causes life-threatening cryptococcal meningitis (CM), especially in regions of the world where AIDS is endemic. The polysaccharide capsule of C. neoformans is the fungus major virulent factor, being copiously released during infection and causing immunosuppressive defects in the host. Although the capsular material is commonly associated with reactive astrocytes in fatal CM, little is known about the molecular and cellular interactions among astroglia and C. neoformans. As astrocytes also make up the neurovascular unit at the blood-brain barrier (BBB), which C. neoformans must transverse to colonize the central nervous system and cause CM; these cells may play a significant regulatory role in the prevention and progression of infection. For example, astrocytes are implicated in neurological disease including the regulation of cerebral intracranial pressure, immune function, and water homeostasis. Hence, in this review, we provide a general overview of astroglia biology and discuss the current knowledge on C. neoformans-astrocyte interactions including their involvement in the development of CM. This "gliocentric view" of cerebral cryptococcosis suggests that therapeutic interventions particularly targeting at preserving the neuroprotective function of astrocytes may be used in preventing and managing C. neoformans BBB transmigration, brain invasion, colonization, and meningitis.