Lack of TLR9 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 (CNS) infection. Toll-like receptor 9 (TLR9) can control cryptococcosis and another mycosis. 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 (VH), and optic nerve (ON) of TLR9-/- mice three weeks after infection. Capsular polysaccharide glucuronoxylomannan (GXM) deposition, astrogliosis and morphological alterations in retina lead to progressive blindness of TLR9-/- mice. The phenomenon observed in our work has not yet been explored 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.