Secreted pH-Regulated Antigen 1 of Candida albicans Blocks Activation and Conversion of Complement C3

Secreted pH-Regulated Antigen 1 of Candida albicans Blocks Activation and Conversion of Complement C3
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白色念珠菌分泌的 pH 调节抗原 1 阻断补体 C3 的激活和转化

DOI:
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发表时间:
2010
影响因子:
4.4
通讯作者:
P. Zipfel
P. Zipfel
中科院分区:
医学2区
文献类型:
--
作者:
Shanshan Luo;A. Hartmann;H. Dahse;C. Skerka;P. Zipfel

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补体系统形成先天免疫的第一道防线,并在感染人类致病性酵母菌白色念珠菌后数秒内被激活。在这项研究中,我们确定了一个新的补体逃避策略使用的C。白色念珠菌。该真菌分泌一种有效的补体抑制剂,pH调节的Ag 1(Pra 1),其在病原体的直接周围结合到液相C3并阻断C3裂解为C3 a和C3 b,如ELISA、天然凝胶电泳和Western印迹所示。因此,通过旁路和经典途径的补体激活被抑制。此外,过敏毒素C3 a和C5 a的释放以及C3 b/iC 3b表面沉积减少,如Western印迹、ELISA、共聚焦显微镜和流式细胞术所示。通过降低酵母表面的C3 b/iC 3b水平,Pra 1降低补体介导的粘附以及C.流式细胞术显示,人巨噬细胞对白色念珠菌的吞噬作用。因此,据我们所知,Pra 1是第一个有效的真菌补体抑制剂,有利于C。白念珠菌通过在C3水平灭活和控制宿主补体攻击而免疫逃逸。
The complement system forms the first defense line of innate immunity and is activated within seconds upon infection by human pathogenic yeast Candida albicans. In this study, we identified a new complement evasion strategy used by C. albicans. The fungus secretes a potent complement inhibitor, pH-regulated Ag 1 (Pra1), which in the direct surrounding of the pathogen binds to fluid-phase C3 and blocks cleavage of C3 to C3a and C3b, as shown by ELISA, native gel electrophoresis, and Western blotting. Consequently, complement activation via the alternative and classical pathways is inhibited. In addition, the release of the anaphylatoxins C3a and C5a, as well as C3b/iC3b surface deposition, is reduced, as demonstrated by Western blotting, ELISA, confocal microscopy, and flow cytometry. By reducing C3b/iC3b levels at the yeast surface, Pra1 decreases complement-mediated adhesion, as well as uptake of C. albicans by human macrophages, as shown by flow cytometry. Thus, Pra1 is, to our knowledge, the first potent fungal complement inhibitor that favors C. albicans immune escape by inactivating and controlling host complement attack at the level of C3.
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发表时间: 1993-06
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