Pathogen-derived extracellular vesicles mediate virulence in the fatal human pathogen Cryptococcus gattii.
Pathogen-derived extracellular vesicles mediate virulence in the fatal human pathogen Cryptococcus gattii.
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DOI：
10.1038/s41467-018-03991-6
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发表时间：
2018-04-19
影响因子：
16.6
通讯作者：
May RC
中科院分区：
文献类型：
--
作者：
Bielska E;Sisquella MA;Aldeieg M;Birch C;O'Donoghue EJ;May RC
由真菌病原体加特隐球菌的近克隆谱系引起的太平洋西北部隐球菌病爆发，代表了目前已知的其他健康人类宿主中最重要的危及生命的真菌感染集群。爆发谱系具有在人类白色血细胞中快速生长的显著能力，使用病原体群体内独特的“劳动分工”机制，其中一些细胞采取休眠行为以支持邻近细胞的生长。在这里，我们表明，致病性的“分工”可以触发在大的细胞距离和介导的真菌细胞外囊泡的释放。由强毒株释放的分离的囊泡被感染的宿主巨噬细胞吸收并运输到吞噬体，在那里它们触发非爆发真菌细胞的快速细胞内生长，否则这些细胞将被宿主消除。因此，长距离病原体-病原体通信通过细胞外囊泡代表了一种新的机制，以控制复杂的毒性表型在隐球菌gattii，并可能，其他传染性物种。真菌病原体隐球菌的高毒性细胞通过刺激邻近真菌细胞的生长而在吞噬细胞内迅速生长。在这里，Bielska等人表明，这种作用是由真菌细胞外囊泡的释放介导的，这些囊泡可以被感染的巨噬细胞吸收。
The Pacific Northwest outbreak of cryptococcosis, caused by a near-clonal lineage of the fungal pathogen Cryptococcus gattii, represents the most significant cluster of life-threatening fungal infections in otherwise healthy human hosts currently known. The outbreak lineage has a remarkable ability to grow rapidly within human white blood cells, using a unique ‘division of labour’ mechanism within the pathogen population, where some cells adopt a dormant behaviour to support the growth of neighbouring cells. Here we demonstrate that pathogenic ‘division of labour’ can be triggered over large cellular distances and is mediated through the release of extracellular vesicles by the fungus. Isolated vesicles released by virulent strains are taken up by infected host macrophages and trafficked to the phagosome, where they trigger the rapid intracellular growth of non-outbreak fungal cells that would otherwise be eliminated by the host. Thus, long distance pathogen-to-pathogen communication via extracellular vesicles represents a novel mechanism to control complex virulence phenotypes in Cryptococcus gattii and, potentially, other infectious species. Highly virulent cells of the fungal pathogen Cryptococcus gattiigrow rapidly within phagocytes by stimulating the growth of neighbouring fungal cells. Here, Bielska et al. show that this effect is mediated by the release of fungal extracellular vesicles that can be taken up by infected macrophages.
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影响因子：
3.1
作者：
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通讯作者：
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影响因子：
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通讯作者：
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