IgG型β-1,6-葡聚糖特异性抗体在治疗白色念珠菌感染中的作用

The therapeutic effect of mouse β-1,6-glucan-specific Ig G on systemic candidasis in mice

目的探讨Ig G型β-1,6-葡聚糖特异性抗体在抗白色念珠菌感染过程中的作用。方法首先通过还原胺法将β-1,6-葡聚糖(pustulan)与载体蛋白牛血清白蛋白(BSA)偶联来免疫小鼠,以制备Ig G型β-1,6-葡聚糖特异性多抗,通过流式细胞术确定该抗体能够很好地识别白色念珠菌表面的β-1,6-葡聚糖。进而,我们通过抗血清过继转移实验进一步研究了Ig G型β-1,6-葡聚糖特异性多抗在抗真菌感染中的作用。结果 1将pustulan与BSA偶联可以有效地诱导Ig G型β-1,6-葡聚糖特异性多抗的产生。2流式结果显示该抗体能够很好地识别白色念珠菌表面的β-1,6-葡聚糖。3抗血清过继转移实验结果显示Ig G型β-1,6-葡聚糖特异性多抗在体内可以明显减少经白色念珠菌感染的小鼠肾脏的真菌载量。4体外抑菌实验结果显示,Ig G型β-1,6-葡聚糖特异性多抗在体外可以较好的抑制真菌的生长。结论 Ig G型β-1,6-葡聚糖特异性抗体具有抗白色念珠菌感染的作用,这可能为真菌感染的诊断与治疗提供新的途径。

As a class of polysaccharides composed of D-glucopyranose monomer, β-glucan is widely expressed on the cell wall of fungi（Candida albicans, yeast, Cryptococcus neoformans, mushrooms and Ganoderma lucidum, etc.） and plants（such as oats, barley, etc.）. β-glucan on the surface of Candida albicans is highly branched, with a backbone of β-1, 3-linked linear glucan and many branches of β-1, 6 glucan. These two structures are both recognized by the immune system as typical pathogen-associated molecular patterns（PAMPs）,and thereby are capable of triggering immune responses. It has been showed that Ig G specific to β-1, 3-glucan antibody posses significant antifungal activities, while Ig M directed against β-1, 6-glucan is ineffective. However,the immune activity of Ig G against β-1, 6-glucan remains unknown. Therefore, in this thesis we generated mouse Ig G Abs specific for β-1, 6-glucan and subsequently explored its role in anti-fungal infection. We firstly generatedβ-1, 6-glucan specific Ig G by coupling pustulan to carrier protein BSA, and confirmed that the antibodies could recognize β-1, 6-glucan expressed on the surface of Candida albicans by flow cytometry and ELISA. Subsequently,we studied the role of Ig G against β-1, 6-glucan in anti-fungal infection both in vivo and in vitro. The results showed that β-1, 6-glucans specific Ig G could not only inhibit the growth of fungi in vitro, but also significantly reduce the fungal invasion in kidneys in vivo. Our results suggested that β-1, 6-glucans specific Ig G can exert therapeutic effect on Candida albicans infection, which may provide a new strategy for the diagnosis and treatment of systemic candidasis.