Phagosorne extrusion and host-cell survival after Cryptococcus neoformans phagocytosis by macrophages
Phagosorne extrusion and host-cell survival after Cryptococcus neoformans phagocytosis by macrophages
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DOI：
10.1016/j.cub.2006.09.061
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发表时间：
2006-11-07
期刊：
影响因子：
9.2
通讯作者：
Casadevall, Arturo
中科院分区：
文献类型：
--
作者：
Alvarez, Mauricio;Casadevall, Arturo
新型隐球菌 (Cn) 是一种有荚膜酵母，是一种兼性细胞内病原体，也是人类疾病的常见原因。 Cn 与肺泡巨噬细胞的相互作用对于遏制感染至关重要 [1, 2]，但 Cn 也可以在细胞内复制并裂解巨噬细胞 [3-5]。 Cn 具有独特的细胞内致病策略，涉及含多糖囊泡的细胞质积累和细胞内复制，导致形成宽敞的吞噬体，其中存在多个隐球菌细胞 [3]。巨噬细胞和阿米巴原虫中的 Cn 细胞内致病策略是相似的，因此有人提出它起源于环境中对抗吞噬捕食者的生存机制 [6]。在这里，我们报告在某些条件下，包括吞噬体成熟、可能的肌动蛋白解聚和同型吞噬体融合，Cn可以通过吞噬体的挤压离开巨噬细胞宿主，而释放的病原体和宿主都保持存活并能够繁殖。 “吞噬体挤出”现象表明存在一种以前未被认识的机制，通过这种机制，真菌病原体可以逃离哺乳动物巨噬细胞的细胞内范围，继续繁殖，并可能进行传播。
Cryptococcus neoformans (Cn) is an encapsulated yeast that is a facultative intracellular pathogen and a frequent cause of human disease. The interaction of Cn with alveolar macrophages is critical for containing the infection [1, 2], but Cn can also replicate intracellularly and lyse macrophages [3-5]. Cn has a unique intracellular pathogenic strategy that involves cytoplasmic accumulation of polysaccharide-containing vesicles and intracellular replication leading to the formation of spacious phagosomes in which multiple cryptococcal cells are present [3]. The Cn intracellular pathogenic strategy in macrophages and amoebas is similar, leading to the proposal that it originated as a mechanism for survival against phagocytic predators in the environment [6]. Here, we report that under certain conditions, including phagosomal maturation, possible actin depolymerization, and homotypic phagosome fusion, Cn can exit the macrophage host through an extrusion of the phagosome, while both the released pathogen and host remain alive and able to propagate. The phenomenon of "phagosomal extrusion" indicates the existence of a previously unrecognized mechanism whereby a fungal pathogen can escape the intracellular confines of mammalian macrophages to continue propagation and, possibly, dissemination.