Novel Structural Features in Candida albicans Hyphal Glucan Provide a Basis for Differential Innate Immune Recognition of Hyphae Versus Yeast
Novel Structural Features in Candida albicans Hyphal Glucan Provide a Basis for Differential Innate Immune Recognition of Hyphae Versus Yeast
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DOI：
10.1074/jbc.m113.529131
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发表时间：
2014-02-07
影响因子：
4.8
通讯作者：
Williams, David L.
中科院分区：
文献类型：
--
作者：
Lowman, Douglas W.;Greene, Rachel R.;Williams, David L.
背景：人类天然免疫系统可以区分白色念珠菌的酵母菌和菌丝菌.结果：C.白色念珠菌菌丝具有菌丝所特有的葡聚糖结构，而在酵母中没有发现。结论：菌丝葡聚糖能增强免疫应答。意义：这些数据为C.先天免疫系统对白色念珠菌酵母菌和菌丝的识别有差异。先天性免疫系统如何有效地区分酵母和菌丝形式的C。白色念珠菌。葡聚糖是真菌细胞壁的主要成分，也是真菌病原体相关的关键分子模式。C.白念珠菌酵母葡聚糖已被鉴定，然而，对C.白色念珠菌菌丝使用一种能最大限度地减少天然结构降解的提取方法，我们从C.白色念珠菌菌丝细胞壁。1H-1 NMR数据分析表明，当与参考（13，16）-连接的葡聚糖和C.白念珠菌酵母葡聚糖，菌丝葡聚糖具有独特的环状或闭合链结构，在酵母葡聚糖中没有发现。GC/MS分析表明，与酵母葡聚糖相比，3-和6-连接的葡萄糖单元丰度高。除了预期的（13），（16）和3，6连锁，我们还确定了一个2，3连锁，以前没有报道过在C。白色念珠菌。菌丝葡聚糖通过Dectin-1依赖性机制在人外周血单核细胞和巨噬细胞中诱导稳健的免疫应答。与此相反，C.白色酵母葡聚糖是一种效力小得多的刺激物。我们还证明了C.白念珠菌菌丝葡聚糖，而不是酵母葡聚糖，诱导IL-1的加工和分泌。这一发现为理解粘膜水平上定植和侵袭之间的免疫区分提供了重要证据。综合起来，这些数据为C.白色念珠菌酵母菌与菌丝。
Background: The human innate immune system can discriminate between Candida albicans yeast and hyphal forms. Results:C. albicans hyphae possess glucan structures that are unique to the hyphae and are not found in yeast. Conclusion: Hyphal glucan elicits robust immune responses. Significance: These data provide a structural basis for differential immune recognition of C. albicans yeast versus hyphae.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. H-1 NMR data analysis revealed that, when compared with reference (13,16) -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 -glucan. In addition to the expected (13), (16), 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-1 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.