Basso A M M, De Castro R J A, de Castro T B, Guimarães H I, Polez V L P, Carbonero E R, Pomin V H, Hoffmann C, Grossi-de-Sa M F, Tavares A H, Bocca A L
Department of Cell Biology, Institute of Biological Sciences, University of Brasília, UnB, Brasilia, DF, Brazil.
Embrapa Genetic Resources and Biotechnology, Brasília, Brazil.
Med Mycol. 2020 Feb 1;58(2):227-239. doi: 10.1093/mmy/myz042.
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 β-(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 β-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.
目前的抗真菌药物疗效不佳，且尚无针对真菌感染的可用疫苗。因此，非常需要治疗或预防侵袭性真菌病（如隐球菌病）的新策略。一种策略是使用从蘑菇中分离出的多糖类免疫调节剂。本研究的目的是评估来自黑木耳的含β-(1,3)-葡聚糖胞外多糖（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与C型凝集素受体家族的模式识别受体Dectin-1结合后，可触发巨噬细胞和树突状细胞的激活。Dectin-1的激活通过其经典的Syk依赖性信号通路，最终导致促炎细胞因子的产生和细胞成熟。此外，经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至M1巨噬细胞模式，这与杀菌分子一氧化氮的产生增加相关，从而有效杀死新型隐球菌。EPS处理还上调了巨噬细胞中与宿主抵御新型隐球菌及Dectin-1介导的信号传导相关的编码产物的基因转录水平。最后，口服来自黑木耳的含β-葡聚糖EPS可提高感染新型隐球菌小鼠的存活率。总之，结果表明黑木耳的EPS在吞噬细胞中发挥免疫刺激活性，并诱导宿主抵御新型隐球菌，提示该蘑菇中的多糖有望作为疫苗佐剂或抗真菌治疗药物。
