Histoplasma capsulatum surmounts obstacles to intracellular pathogenesis.
Histoplasma capsulatum surmounts obstacles to intracellular pathogenesis.
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DOI：
10.1111/febs.13389
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发表时间：
2016-02
期刊：
影响因子：
--
通讯作者：
Rappleye CA
中科院分区：
文献类型：
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作者：
Garfoot AL;Rappleye CA
真菌病原体组织胞浆菌会引起呼吸道和播散性疾病，甚至在免疫能力强的宿主中也是如此。与容易被吞噬细胞控制的机会性病原体不同，胶囊H。在这篇综述中，我们讨论了一些分子机制，使幽门螺杆菌酵母菌克服障碍的细胞内致病。胶囊酵母通过利用吞噬细胞受体的β-整合素家族来促进进入巨噬细胞，从而躲避细胞外的障碍，如抗菌肺表面活性蛋白。此外，胶囊酵母隐藏免疫刺激的β-葡聚糖，以避免触发信号受体，如β-葡聚糖受体Dectin-1。胶囊酵母通过表达氧化应激防御酶，包括胞外超氧化物歧化酶和胞外过氧化氢酶，来对抗吞噬细胞产生的活性氧物种。在吞噬小体内，胶囊酵母阻止吞噬小体的酸化，获得铁和锌等必需金属，并利用从头合成途径来克服营养限制。这些机制解释了包膜酵母菌如何避免和否定巨噬细胞的防御策略，并建立了一个友好的细胞内生态位，使包膜杆菌成为成功的巨噬细胞内病原体。
The fungal pathogen Histoplasma capsulatum causes respiratory and disseminated disease, even in immunocompetent hosts. In contrast to opportunistic pathogens, which are readily controlled by phagocytic cells, H. capsulatum yeasts are able to infect macrophages, survive antimicrobial defenses, and proliferate as an intracellular pathogen. In this review, we discuss some of the molecular mechanisms that enable H. capsulatum yeasts to overcome obstacles to intracellular pathogenesis. H. capsulatum yeasts gain refuge from extracellular obstacles such as antimicrobial lung surfactant proteins by engaging the β-integrin family of phagocytic receptors to promote entry into macrophages. In addition, H. capsulatum yeasts conceal immunostimulatory β-glucans to avoid triggering signaling receptors such as the β-glucan receptor Dectin-1. H. capsulatum yeasts counteract phagocyte-produced reactive oxygen species by expression of oxidative stress defense enzymes including an extracellular superoxide dismutase and an extracellular catalase. Within the phagosome, H. capsulatum yeasts block phagosome acidification, acquire essential metals such as iron and zinc, and utilize de novo biosynthesis pathways to overcome nutritional limitations. These mechanisms explain how H. capsulatum yeasts avoid and negate macrophage defense strategies and establish a hospitable intracellular niche, making H. capsulatum a successful intracellular pathogen of macrophages.