Effects on microglial morphology and function following CNS colonization by C. neoformans and its GXM capsule

Cryptococcus neoformans is an encapsulated basidiomycete fungus that has a predilection for the CNS, causing cryptococcal meningoencephalitis. This disease is most common in immunocompromised individuals such as patients with HIV+ or on immunosuppressive regimens. The fungus is inhaled from pigeon droppings and Eucalyptus tree bark. Once inhaled, the fungus travels from the airway into the bloodstream where it travels systemically into the CNS. It has acquired three main ways of crossing the blood-brain barrier, but questions still exist about the dynamics of how the fungus colonizes the brain and how the host responds to this colonization. The fungus has three main virulence factors that allow it to colonize its hosts: antioxidant melanin production, immune-modulatory GXM polysaccharide capsule, and the ability to withstand physiological temperatures. Focusing on the effect of GXM, we saw that infection with the capsular H99 strain of C. neoformans, there was a decrease in mortality, while fungal burden and microglial migration to the cryptococcoma rose. There were also morphological changes in these microglial, so transcriptomics and functional migration and phagocytosis assays were conducted to evaluate the cellular activities at the site of infection. In summary, although microglia migrated and were recruited to the site of infection by the upregulation of pro-inflammatory pathways, they were unable to exert their functional roles due to a stonewall effect by GXM, as demonstrated by a reduction in migration to and phagocytosis of the fungus.