Alvarez Mauricio, Casadevall Arturo
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, 10461, USA.
Curr Biol. 2006 Nov 7;16(21):2161-5. doi: 10.1016/j.cub.2006.09.061.
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 , but Cn can also replicate intracellularly and lyse macrophages . 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 . 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 . 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.
新型隐球菌（Cn）是一种有荚膜的酵母，是兼性细胞内病原体，也是人类疾病的常见病因。Cn与肺泡巨噬细胞的相互作用对于控制感染至关重要，但Cn也能在细胞内复制并裂解巨噬细胞。Cn有一种独特的细胞内致病策略，包括含多糖囊泡的细胞质积累和细胞内复制，导致形成含有多个隐球菌细胞的宽敞吞噬体。Cn在巨噬细胞和变形虫中的细胞内致病策略相似，这表明它最初是作为一种在环境中抵御吞噬性捕食者的生存机制。在此，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可通过吞噬体挤出而离开巨噬细胞宿主，而释放出的病原体和宿主均保持存活并能够繁殖。“吞噬体挤出”现象表明存在一种先前未被认识的机制，通过该机制真菌病原体可逃离哺乳动物巨噬细胞的细胞内限制，以继续繁殖并可能传播。
