From the Department of Surgery and.
J Biol Chem. 2014 Feb 7;289(6):3432-43. doi: 10.1074/jbc.M113.529131. Epub 2013 Dec 16.
The innate immune system differentially recognizes Candida albicans yeast and hyphae. It is not clear how the innate immune system effectively discriminates between yeast and hyphal forms of C. albicans. Glucans are major components of the fungal cell wall and key fungal pathogen-associated molecular patterns. C. albicans yeast glucan has been characterized; however, little is known about glucan structure in C. albicans hyphae. Using an extraction procedure that minimizes degradation of the native structure, we extracted glucans from C. albicans hyphal cell walls. (1)H NMR data analysis revealed that, when compared with reference (1→3,1→6) β-linked glucans and C. albicans yeast glucan, hyphal glucan has a unique cyclical or "closed chain" structure that is not found in yeast glucan. GC/MS analyses showed a high abundance of 3- and 6-linked glucose units when compared with yeast β-glucan. In addition to the expected (1→3), (1→6), and 3,6 linkages, we also identified a 2,3 linkage that has not been reported previously in C. albicans. Hyphal glucan induced robust immune responses in human peripheral blood mononuclear cells and macrophages via a Dectin-1-dependent mechanism. In contrast, C. albicans yeast glucan was a much less potent stimulus. We also demonstrated the capacity of C. albicans hyphal glucan, but not yeast glucan, to induce IL-1β processing and secretion. This finding provides important evidence for understanding the immune discrimination between colonization and invasion at the mucosal level. When taken together, these data provide a structural basis for differential innate immune recognition of C. albicans yeast versus hyphae.
天然免疫系统可区分白色念珠菌的酵母相和菌丝相。但目前尚不清楚天然免疫系统如何有效区分白色念珠菌的酵母相和菌丝相。葡聚糖是真菌细胞壁的主要成分，也是关键的真菌病原体相关分子模式。已对白色念珠菌酵母葡聚糖的结构进行了研究；然而，对于白色念珠菌菌丝葡聚糖的结构却知之甚少。我们采用一种能最大程度减少天然结构降解的提取方法，从白色念珠菌菌丝细胞壁中提取葡聚糖。（1）H NMR 数据分析表明，与参考（1→3,1→6）β 连接葡聚糖和白色念珠菌酵母葡聚糖相比，菌丝葡聚糖具有独特的环状或“封闭链”结构，而这种结构在酵母葡聚糖中是不存在的。GC/MS 分析显示，与酵母 β-葡聚糖相比，3-和 6-连接的葡萄糖单位含量较高。除了预期的（1→3）、（1→6）和 3,6 键之外，我们还鉴定出了一种 2,3 键，这在以前的白色念珠菌中尚未报道过。与白色念珠菌酵母葡聚糖相比，菌丝葡聚糖通过 Dectin-1 依赖性机制诱导人外周血单核细胞和巨噬细胞产生强烈的免疫反应。此外，我们还证明了白色念珠菌菌丝葡聚糖（而非酵母葡聚糖）能够诱导 IL-1β 加工和分泌。这一发现为理解黏膜水平定植与侵袭之间的免疫区分提供了重要依据。总之，这些数据为白色念珠菌酵母相和菌丝相的天然免疫识别提供了结构基础。
