Graduate Program in Molecular Pathology, Faculty of Medicine, University of Brasília, UnB, Brasília, DF, Brazil.
Faculty of Ceilândia, University of Brasília, UnB, Brasília, DF, Brazil.
Med Mycol. 2021 Jul 14;59(8):749-762. doi: 10.1093/mmy/myaa117.
Paracoccidioides brasiliensis is the major etiologic agent of Paracoccidioidomycosis (PCM), the most frequent human deep mycosis in Latin America. It is proposed that masking of β-glucan in P. brasiliensis cell wall is a critical virulence factor that contributes to the development of a chronic disease characterized by a long period of treatment, which is usually toxic. In this context, the search for immunomodulatory agents for therapeutic purposes is highly desirable. One strategy is to use pattern recognition receptors (PRRs) ligands to stimulate the immune response mediated by phagocytes. Here, we sought to evaluate if Zymosan, a β-glucan-containing ligand of the PRRs Dectin-1/TLR-2, would enhance phagocyte function and the immune response of mice challenged with P. brasiliensis. Dendritic cells (DCs) infected with P. brasiliensis and treated with Zymosan showed improved secretion of several proinflammatory cytokines and expression of maturation markers. In addition, when cocultured with splenic lymphocytes, these cells induced the production of a potential protective type 1 and 17 cytokine patterns. In macrophages, Zymosan ensued a significant fungicidal activity associated with nitric oxide production and phagolysosome acidification. Importantly, we observed a protective effect of Zymosan-primed DCs delivered intranasally in experimental pulmonary PCM. Overall, our findings support the potential use of β-glucan-containing compounds such as Zymosan as an alternative or complementary antifungal therapy.
We report for the first time that Paracoccidioides brasiliensis-infected phagocytes treated with Zymosan (cell wall extract from bakers' yeast) show enhanced cytokine production, maturation, and fungal killing. Also, Zymosan-primed phagocytes induce a protective immune response in infected mice.
巴西副球孢子菌是巴西副球孢子菌病（PCM）的主要病原体，这是拉丁美洲最常见的人类深部真菌病。据推测，巴西副球孢子菌细胞壁中β-葡聚糖的掩蔽是一个关键的毒力因子，导致慢性疾病的发展，这种疾病通常具有较长的治疗期和毒性。在这种情况下，迫切需要寻找免疫调节剂用于治疗目的。一种策略是使用模式识别受体（PRR）配体来刺激吞噬细胞介导的免疫反应。在这里，我们试图评估β-葡聚糖包含的 PRR Dectin-1/TLR-2 配体 Zymosan 是否会增强吞噬细胞的功能和对巴西副球孢子菌挑战的小鼠的免疫反应。感染巴西副球孢子菌并用 Zymosan 处理的树突状细胞（DC）显示出几种促炎细胞因子分泌和成熟标志物表达的改善。此外，当与脾淋巴细胞共培养时，这些细胞诱导产生潜在的保护性 1 型和 17 型细胞因子模式。在巨噬细胞中，Zymosan 导致与一氧化氮产生和吞噬体酸化相关的显著杀真菌活性。重要的是，我们观察到经鼻内给予 Zymosan 预刺激的 DC 在实验性肺 PCM 中的保护作用。总的来说，我们的研究结果支持使用含β-葡聚糖的化合物（如 Zymosan）作为替代或补充抗真菌治疗的潜力。
我们首次报道，用 Zymosan（来自面包酵母的细胞壁提取物）处理的巴西副球孢子菌感染的吞噬细胞显示出增强的细胞因子产生、成熟和真菌杀伤作用。此外，Zymosan 预刺激的吞噬细胞在感染小鼠中诱导保护性免疫反应。
