Department of Dermatology, Eberhard Karls University Tübingen, Tübingen, Germany.
PLoS One. 2012;7(11):e50518. doi: 10.1371/journal.pone.0050518. Epub 2012 Nov 30.
C. albicans is one of the most common fungal pathogen of humans, causing local and superficial mucosal infections in immunocompromised individuals. Given that the key structure mediating host-C. albicans interactions is the fungal cell wall, we aimed to identify features of the cell wall inducing epithelial responses and be associated with fungal pathogenesis. We demonstrate here the importance of cell wall protein glycosylation in epithelial immune activation with a predominant role for the highly branched N-glycosylation residues. Moreover, these glycan moieties induce growth arrest and apoptosis of epithelial cells. Using an in vitro model of oral candidosis we demonstrate, that apoptosis induction by C. albicans wild-type occurs in early stage of infection and strongly depends on intact cell wall protein glycosylation. These novel findings demonstrate that glycosylation of the C. albicans cell wall proteins appears essential for modulation of epithelial immunity and apoptosis induction, both of which may promote fungal pathogenesis in vivo.
白色念珠菌是人类最常见的真菌病原体之一,在免疫功能低下的个体中引起局部和浅表黏膜感染。鉴于介导宿主-白色念珠菌相互作用的关键结构是真菌细胞壁,我们旨在确定诱导上皮反应并与真菌发病机制相关的细胞壁特征。我们在这里证明了细胞壁蛋白糖基化在上皮免疫激活中的重要性,其中高度分支的 N-糖基化残基起着主要作用。此外,这些聚糖片段诱导上皮细胞生长停滞和凋亡。我们使用口腔念珠菌病的体外模型证明,白色念珠菌野生型诱导的细胞凋亡发生在感染的早期阶段,并且强烈依赖于完整的细胞壁蛋白糖基化。这些新发现表明,白色念珠菌细胞壁蛋白的糖基化对于调节上皮免疫和凋亡诱导至关重要,这两者都可能促进体内真菌发病机制。