Lack of Toll-Like Receptor 9 Exacerbates Ocular Impairment and Visual Loss During Systemic Cryptococcus gattii Infection.

Abstract

Cryptococcus gattii is a saprophytic basidiomycete that grows in the environment and can cause systemic cryptococcosis. Ocular cryptococcosis causes blindness and is commonly associated with central nervous system infection. Toll-like receptor 9 (TLR9) can control cryptococcosis and other mycoses. Here, using C57BL/6 TLR9 knockout mice (TLR9-/-), we evaluated the role of TLR9 signaling in ocular involvement during systemic C. gattii infection. We observed ocular impairment and found a high fungal burden in the retina, vitreous humor, and optic nerve of TLR9-/- mice 3 weeks after infection. Capsular polysaccharide glucuronoxylomannan deposition, astrogliosis, and morphological alterations in retina led to progressive blindness of TLR9-/- mice. The phenomenon observed in our work had not been explored previously in a murine model. These results contribute to the understanding of the role of TLR9 during ocular cryptococcosis. Therapies using TLR9 agonists may be important for the treatment of ocular cryptococcosis.