Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-900, Brazil.
Laboratório de Imunoparasitologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, 21045-900, Brazil.
Sci Rep. 2018 Nov 6;8(1):16378. doi: 10.1038/s41598-018-34649-4.
Cryptococcus neoformans is an opportunistic fungus that can cause lethal brain infections in immunosuppressed individuals. Infection usually occurs via the inhalation of a spore or desiccated yeast which can then disseminate from the lung to the brain and other tissues. Dissemination and disease is largely influence by the production of copious amounts of cryptococcal polysaccharides, both which are secreted to the extracellular environment or assembled into a thick capsule surrounding the cell body. There are two important polysaccharides: glucuronoxylomannan (GXM) and galactoxylomannan, also called as glucuronoxylomanogalactan (GXMGal or GalXM). Although GXM is more abundant, GalXM has a more potent modulatory effect. In the present study, we show that GalXM is a potent activator of murine dendritic cells, and when co-cultured with T cells, induces a Th17 cytokine response. We also demonstrated that treating mice with GalXM prior to infection with C. neoformans protects from infection, and this phenomenon is dependent on IL-6 and IL-17. These findings help us understand the immune biology of capsular polysaccharides in fungal pathogenesis.
新型隐球菌是一种机会性真菌，可在免疫抑制个体中引起致命性脑部感染。感染通常通过吸入孢子或干燥酵母发生，然后从肺部传播到大脑和其他组织。传播和疾病在很大程度上受大量隐球菌多糖的产生影响，这些多糖既分泌到细胞外环境中，也组装成围绕细胞体的厚荚膜。有两种重要的多糖：葡聚糖甘露聚糖 (GXM) 和半乳甘露聚糖，也称为葡聚糖甘露寡糖 (GXMGal 或 GalXM)。虽然 GXM 更为丰富，但 GalXM 具有更强的调节作用。在本研究中，我们表明 GalXM 是一种有效的小鼠树突状细胞激活剂，并且与 T 细胞共培养时会诱导 Th17 细胞因子反应。我们还证明，在感染新型隐球菌之前用 GalXM 处理小鼠可预防感染，而这种现象依赖于 IL-6 和 IL-17。这些发现有助于我们了解荚膜多糖在真菌发病机制中的免疫生物学。
