'Division of labour' in response to host oxidative burst drives a fatal Cryptococcus gattii outbreak.
'Division of labour' in response to host oxidative burst drives a fatal Cryptococcus gattii outbreak.
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DOI：
10.1038/ncomms6194
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发表时间：
2014-10-17
影响因子：
16.6
通讯作者：
May, Robin C.
中科院分区：
文献类型：
--
作者：
Voelz, Kerstin;Johnston, Simon A.;Smith, Leanne M.;Hall, Rebecca A.;Idnurm, Alexander;May, Robin C.
格特隐球菌是一种新兴的细胞内病原体，是健康人群中最大的危及生命的真菌疾病原发性爆发的原因。爆发菌株共享一个独特的线粒体基因表达谱和增加的能力，微管化其线粒体内的宿主巨噬细胞。然而，导致C. gattii在免疫功能正常的个体中具有毒性仍然无法解释。在这里，我们表明，一个亚群的细胞内C。gattii采用管状线粒体形态以响应宿主活性氧。这些真菌细胞然后促进邻近的C. gattii细胞与非管状线粒体，允许病原体有效地建立在巨噬细胞内的小生境。因此，宿主活性氧物质，先天免疫反应的重要组成部分，作为主要的信号分子，引发细胞内真菌种群的“分工”，导致这种爆发谱系内的发病机制增加。 病原真菌格特隐球菌的爆发菌株显示出形成管状线粒体的能力增加。Voelz等人的研究表明，线粒体微管化是由巨噬细胞内的宿主活性氧诱导的，并促进邻近真菌细胞的快速生长。
Cryptococcus gattii is an emerging intracellular pathogen and the cause of the largest primary outbreak of a life-threatening fungal disease in a healthy population. Outbreak strains share a unique mitochondrial gene expression profile and an increased ability to tubularize their mitochondria within host macrophages. However, the underlying mechanism that causes this lineage of C. gattii to be virulent in immunocompetent individuals remains unexplained. Here we show that a subpopulation of intracellular C. gattii adopts a tubular mitochondrial morphology in response to host reactive oxygen species. These fungal cells then facilitate the rapid growth of neighbouring C. gattii cells with non-tubular mitochondria, allowing for effective establishment of the pathogen within a macrophage intracellular niche. Thus, host reactive oxygen species, an essential component of the innate immune response, act as major signalling molecules to trigger a ‘division of labour’ in the intracellular fungal population, leading to increased pathogenesis within this outbreak lineage. Outbreak strains of the pathogenic fungus Cryptococcus gattii display an increased ability to form tubular mitochondria. Here, Voelz et al. show that mitochondrial tubularization is induced by host reactive oxygen species within macrophages and facilitates rapid growth of neighbouring fungal cells.
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