Cryptococcus neoformans interactions with amoebae suggest an explanation for its virulence and intracellular pathogenic strategy in macrophages
Cryptococcus neoformans interactions with amoebae suggest an explanation for its virulence and intracellular pathogenic strategy in macrophages
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DOI：
10.1073/pnas.261418798
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发表时间：
2001-12-18
影响因子：
11.1
通讯作者：
Casadevall, A
中科院分区：
文献类型：
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作者：
Steenbergen, JN;Shuman, HA;Casadevall, A
新型隐球菌（Cn）是一种土壤真菌，在免疫功能低下的患者中引起危及生命的脑膜炎，并且是一种能够在巨噬细胞内复制的兼性细胞内病原体。环境真菌获得和维持对哺乳动物宿主的毒力的机制尚不清楚。我们假设，Cn的生存策略后，吞噬巨噬细胞和阿米巴是相似的。显微镜检查、真菌和阿米巴杀灭试验以及吞噬试验表明，Cn被卡氏阿米巴吞噬并在卡氏阿米巴中复制，从而导致阿米巴死亡。一个acapsular菌株的Cn没有生存时，培养阿米巴，但黑化保护这些细胞对阿米巴杀死。与同基因型菌株相比，磷脂酶突变体在阿米巴中的复制率降低。这些观察结果表明，隐球菌的特点，有助于哺乳动物的毒力也促进真菌的生存阿米巴。胞内复制伴随着积累的多糖含有囊泡类似于那些描述在Cn感染的巨噬细胞。结果表明，CN对哺乳动物细胞的毒力是一个适应的结果，已经演变为保护环境的捕食者，如阿米巴原虫，并提供了一个解释这种致病真菌的广泛的宿主范围。
Cryptococcus neoformans (Cn) is a soil fungus that causes life-threatening meningitis in immunocompromised patients and is a facultative intracellular pathogen capable of replication inside macrophages. The mechanism by which environmental fungi acquire and maintain virulence for mammalian hosts is unknown. We hypothesized that the survival strategies for Cn after ingestion by macrophages and amoebae were similar. Microscopy, fungal and amoebae killing assays, and phagocytosis assays revealed that Cn is phagocytosed by and replicates in Acanthamoeba castellanii, which leads to death of amoebae. An acapsular strain of Cn did not survive when incubated with amoebae, but melanization protected these cells against killing by amoebae. A phospholipase mutant had a decreased replication rate in amoebae compared with isogenic strains. These observations suggest that cryptococcal characteristics that contribute to mammalian virulence also promote fungal survival in amoebae. Intracellular replication was accompanied by the accumulation of polysaccharide containing vesicles similar to those described in Cn-infected macrophages. The results suggest that the virulence of Cn for mammalian cells is a consequence of adaptations that have evolved for protection against environmental predators such as amoebae and provide an explanation for the broad host range of this pathogenic fungus.