da Silva-Junior Elias Barbosa, Araújo Victor Guedes, Araujo-Silva Carlla Assis, Covre Luciana Polaco, Guimarães-de-Oliveira Joyce Cristina, Diniz-Lima Israel, Freire-de-Lima Leonardo, Morrot Alexandre, de Brito-Gitirana Lycia, Previato Jose Osvaldo, Mendonça-Previato Lucia, Vommaro Rossiane Claudia, Petrs-Silva Hilda, Decote-Ricardo Debora, de Matos Guedes Herbert Leonel, Freire-de-Lima Celio Geraldo
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Departamento de Doenças Infecciosas, Universidade Federal do Espírito Santo, Espirito Santo, Brazil.
J Infect Dis. 2025 Jul 11;231(6):1597-1608. doi: 10.1093/infdis/jiaf034.
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.
加氏隐球菌是一种腐生性担子菌，生长于环境中，可引起系统性隐球菌病。眼部隐球菌病可导致失明，通常与中枢神经系统感染相关。Toll样受体9（TLR9）可控制隐球菌病及其他真菌病。在此，我们使用C57BL/6 TLR9基因敲除小鼠（TLR9-/-），评估了TLR9信号在系统性加氏隐球菌感染期间眼部受累过程中的作用。我们观察到眼部损伤，并在感染3周后的TLR9-/-小鼠的视网膜、玻璃体液和视神经中发现了高真菌负荷。荚膜多糖葡糖醛酸木聚糖甘露聚糖沉积、星形胶质细胞增生以及视网膜形态学改变导致TLR9-/-小鼠逐渐失明。我们工作中观察到的这一现象此前在小鼠模型中尚未得到研究。这些结果有助于理解TLR9在眼部隐球菌病中的作用。使用TLR9激动剂进行治疗可能对眼部隐球菌病的治疗具有重要意义。
