Candida albicans phospholipomannan promotes survival of phagocytosed yeasts through modulation of bad phosphorylation and macrophage apoptosis
Candida albicans phospholipomannan promotes survival of phagocytosed yeasts through modulation of bad phosphorylation and macrophage apoptosis
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DOI：
10.1074/jbc.m210680200
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发表时间：
2003-04-11
影响因子：
4.8
通讯作者：
Jouault, T
中科院分区：
文献类型：
--
作者：
Ibata-Ombetta, S;Idziorek, T;Jouault, T
致病性酵母白色念珠菌的表面涂覆有磷脂甘露聚糖（PLM），磷脂甘露聚糖是由β-1，2-寡甘露糖苷和植物神经酰胺组成的遗传学上独特的糖脂。本研究比较了PLM对与C.与酿酒酵母相比，巨噬细胞中存在白色念珠菌。C. J774的内吞作用和ERK 1/2信号转导通路的失调与下游Bad Ser-112磷酸化的减少和游离Bcl-2的消失有关。这表明了凋亡效应，这通过巨噬细胞外膜中的磷脂酰丝氨酸染色来证实。将PLM加入到与S.酿酒酵母模拟了用C. albicans，促进S.啤酒。外化膜磷脂酰丝氨酸，线粒体完整性的损失，并诱导PLM的DNA片段化表明，这种分子通过诱导宿主细胞死亡促进酵母的生存。这些结果强烈地表明PLM是C.白色念珠菌的结构和细胞凋亡活性之间的关系的阐明是一个创新的研究领域。
The surface of the pathogenic yeast Candida albicans is coated with phospholipomannan (PLM), a phylogenetically unique glycolipid composed of beta-1,2-oligomannosides and phytoceramide. This study compared the specific contribution of PLM to the modulation of signaling pathways linked to the survival of C. albicans in macrophages in contrast to Saccharomyces cerevisiae. C. albicans endocytosis by J774 and disregulation of the ERK1/2 signal transduction pathway was associated downstream with a reduction in Bad Ser-112 phosphorylation and disappearance of free Bcl-2. This suggested an apoptotic effect, which was confirmed by staining of phosphatidylserine in the macrophage outer membrane. The addition of PLM to macrophages incubated with S. cerevisiae mimicked each of the disregulation steps observed with C. albicans and promoted the survival of S. cerevisiae. Externalization of membranous phosphatidylserine, loss of mitochondrial integrity, and DNA fragmentation induced by PLM showed that this molecule promoted yeast survival by inducing host cell death. These findings suggest strongly that PLM is a virulence attribute of C. albicans and that elucidation of the relationship between structure and apoptotic activity is an innovative field of research.