Cryptococcus neoformans invasion of the orbital compartment and periocular spaces following intracerebral infection in mice.

Cryptococcus neoformans is an encapsulated and neurotropic fungus known for causing life-threatening meningoencephalitis in immunocompromised individuals. We used a murine intracerebral infection model to study C. neoformans brain infection and microglia-fungal interactions. Mice infected with the C. neoformans H99 strain exhibited hydrocephalus, cryptococcoma formation, and significantly higher brain fungal burden than the acapsular cap59 strain at 7-days post infection (dpi). Immunofluorescence imaging showed robust microgliosis, especially near cryptococcomas. Cytokine analysis revealed a host response consistent with brain tissue injury after C. neoformans H99 infection at 3 and 7 dpi. C. neoformans H99 presence and capsular polysaccharide secretion were observed in the orbital compartment and various periocular and extraocular structures, demonstrating a potential infection route between the basal ganglia and ocular tissue. Our results suggest that C. neoformans invasion of the orbital compartment from brain tissue is a complication of cerebral cryptococcosis that may affect treatment and promote relapse.