Laboratory for Immunopharmacology of Microbial Products School of Pharmacy Tokyo University of Pharmacy and Life Sciences 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
Int J Med Mushrooms. 2021;23(2):13-28. doi: 10.1615/IntJMedMushrooms.2020037471.
The edible mushroom Agaricus brasiliensis contains a large amount β-glucan, which is mainly composed of a β-1,6-glucan structure. In this study, we investigated the effect of A. brasiliensis strain KA21 on the anti-β-glucan antibody titer in healthy humans and the role of antibodies as an immunomodulator. Twenty-two healthy volunteers were fed the dried fruiting body of A. brasiliensis (900 or 1500 mg/day) for 12 weeks. The anti-β-glucan antibody titer in the serum was determined by enzyme-linked immunosorbent assay. Immunoglobulin G (IgG) against β-glucan was significantly upregulated after intake of A. brasiliensis. Murine experiments demonstrated improvement of anti-β-glucan antibody production after intraperitoneal injection of Agaricus-derived β-glucan. To understand the role of antibody against β-glucan in exclusion of pathogenic fungi, we examined the interaction between HL-60 cells and antibody-treated heat-killed Candida albicans. Flow cytometry analysis indicated the upregulation of Candida-positive HL-60 cells after treatment with human IgG, whereas the competitive assay demonstrated that the main epitope of Candida-reacted IgG was the β-1,6-glucan structure. Binding between HL-60 and IgG-opsonized C. albicans was suppressed by anti-Fcγ receptor 1 (FcγRI) neutralizing antibody. Finally, using FcγRI-expressed cells with the nuclear factor of activated T-cell reporter assay, we demonstrated that higher titers of anti-β-glucan IgG can induce stronger Fc receptor-mediated cell activation through the formation of an antibody-β-glucan complex. In conclusion, oral ingestion of A. brasiliensis KA21 promotes anti-β-glucan antibody production and may contribute to preventing fungal infection through the activation of immune cells by forming antibody-β-glucan complexes via an FcγR-dependent pathway.
巴西蘑菇含有大量β-葡聚糖,主要由β-1,6-葡聚糖结构组成。本研究旨在探讨巴西蘑菇 KA21 菌株对健康人群抗β-葡聚糖抗体滴度的影响,以及抗体作为免疫调节剂的作用。22 名健康志愿者连续 12 周每天服用巴西蘑菇干实体(900 或 1500mg/天)。通过酶联免疫吸附试验测定血清中抗β-葡聚糖抗体滴度。摄入巴西蘑菇后,IgG 对β-葡聚糖的抗体显著上调。腹腔注射蘑菇来源的β-葡聚糖可改善抗β-葡聚糖抗体的产生。为了了解抗β-葡聚糖抗体在排除致病性真菌中的作用,我们研究了 HL-60 细胞与抗体处理的热灭活白色念珠菌之间的相互作用。流式细胞术分析表明,用人类 IgG 处理后,Candida 阳性 HL-60 细胞的表达上调,而竞争试验表明,与 Candida 反应的 IgG 的主要表位是β-1,6-葡聚糖结构。抗 Fcγ 受体 1(FcγRI)中和抗体抑制了 HL-60 与 IgG 调理的白色念珠菌之间的结合。最后,通过用核因子活化 T 细胞报告基因测定表达 FcγRI 的细胞,我们证明了更高滴度的抗β-葡聚糖 IgG 可以通过形成抗体-β-葡聚糖复合物诱导更强的 Fc 受体介导的细胞激活,从而激活 T 细胞。总之,口服巴西蘑菇 KA21 可促进抗β-葡聚糖抗体的产生,并可能通过形成抗体-β-葡聚糖复合物通过 FcγR 依赖性途径激活免疫细胞,从而有助于预防真菌感染。