Elucidating the Interactions of Cryptococcus Neoformans and Microglia

The encapsulated fungus Cryptococcus neoformans is the most common cause of fungal meningitis, with the highest rate of cryptococcosis found in AIDS patients. Despite antifungal treatment, cryptococcal meningitis is known for its high morbidity and mortality rates due to its difficult eradication from the brain. C. neoformans’ capsule contributes directly to its pathogenesis; specifically, its main component, glucuronoxylomannan (GXM), has been associated with disruption of the blood-brain barrier (BBB) and invasion of the brain. Microglia are the main form of active immune defense in the central nervous system (CNS). These cells are critical for combating CNS-invading microbes, including C. neoformans, but the specific function(s) of microglia required to counteract GXM’s BBB damage and C. neoformans invasion is/are poorly understood. Identification of the mechanisms by which C. neoformans GXM alters the BBB integrity and microglia cell functions will provide novel insights into the neurotropism of this deadly infection and may offer new therapeutic opportunities and preventive measures for combating cerebral cryptococcosis, a disease that kills ~200,000 AIDS patients annually around the world.

Learning objectives:

1. Outline the impact of fungal brain infections on susceptible hosts.

2. Define the virulence factors of Cryptococcus neoformans.

3. Describe the effects of C. neoformans capsule on microglial responses and function.