Immunomodulatory activity of β-glucan-containing exopolysaccharides from Auricularia auricular in phagocytes and mice infected with Cryptococcus neoformans
Immunomodulatory activity of β-glucan-containing exopolysaccharides from Auricularia auricular in phagocytes and mice infected with Cryptococcus neoformans
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DOI：
10.1093/mmy/myz042
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发表时间：
2020-02-01
期刊：
影响因子：
2.9
通讯作者：
Bocca, A. L.
中科院分区：
文献类型：
--
作者：
Basso, A. M. M.;De Castro, R. J. A.;Bocca, A. L.
目前的抗真菌药物效果不佳，并且没有针对真菌感染的疫苗。因此，非常需要治疗或预防侵袭性真菌病（例如隐球菌病）的新策略。一种策略是使用从蘑菇中分离的多糖性质的免疫调节剂。本工作的目的是评估食用菌木耳中含有 β-(1,3)-葡聚糖的胞外多糖 (EPS) 对感染新型隐球菌的吞噬细胞和小鼠的免疫刺激活性。 EPS 在与 Dectin-1（C 型凝集素受体家族的一种模式识别受体）结合后触发巨噬细胞和树突状细胞激活。 Dectin-1 的参与通过其典型的 Syk 依赖性途径信号传导最终导致促炎细胞因子的产生和细胞成熟。此外，在 EPS 处理后，已知支持新型隐球菌细胞内存活和复制的 M2 样表型巨噬细胞会重新极化为 M1 巨噬细胞模式，这与杀菌分子一氧化氮的产生增强相关，从而有效杀死新型隐球菌。 EPS 治疗还上调了编码与宿主针对新型隐球菌的保护相关的产物的基因的转录水平，以及巨噬细胞中 Dectin-1 介导的信号传导。最后，口服来自耳形球囊菌的含有β-葡聚糖的EPS可提高感染新型隐球菌的小鼠的存活率。总之，结果表明，来自木耳的 EPS 在吞噬细胞中发挥免疫刺激活性，并诱导宿主针对新型隐球菌的保护，这表明来自这种蘑菇的多糖可能有希望作为疫苗或抗真菌治疗的佐剂。
Current antifungal drugs present poor effectiveness and there is no available vaccine for fungal infections. Thus, novel strategies to treat or prevent invasive mycosis, such as cryptococcosis, are highly desirable. One strategy is the use of immunomodulators of polysaccharide nature isolated from mushrooms. The purpose of the present work was to evaluate the immunostimulatory activity of beta-(1,3)-glucan-containing exopolysaccharides (EPS) from the edible mushrooms Auricularia auricula in phagocytes and mice infected with Cryptococcus neoformans. EPS triggered macrophages and dendritic cell activation upon binding to Dectin-1, a pattern recognition receptor of the C-type lectin receptor family. Engagement of Dectin-1 culminated in pro-inflammatory cytokine production and cell maturation via its canonical Syk-dependent pathway signaling. Furthermore, upon EPS treatment, M2-like phenotype macrophages, known to support intracellular survival and replication of C. neoformans, repolarize to M1 macrophage pattern associated with enhanced production of the microbicidal molecule nitric oxide that results in efficient killing of C. neoformans. Treatment with EPS also upregulated transcript levels of genes encoding products associated with host protection against C. neoformans and Dectin-1 mediated signaling in macrophages. Finally, orally administrated beta-glucan-containing EPS from A. auricular enhanced the survival of mice infected with C. neoformans. In conclusion, the results demonstrate that EPS from A. auricula exert immunostimulatory activity in phagocytes and induce host protection against C. neoformans, suggesting that polysaccharides from this mushroom may be promising as an adjuvant for vaccines or antifungal therapy.