Cryptococcus neoformans is a facultative intracellular pathogen in murine pulmonary infection
Cryptococcus neoformans is a facultative intracellular pathogen in murine pulmonary infection
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DOI：
10.1128/iai.68.7.4225-4237.2000
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发表时间：
2000-07-01
影响因子：
3.1
通讯作者：
Casadevall, A
中科院分区：
文献类型：
--
作者：
Feldmesser, M;Kress, Y;Casadevall, A
为了产生慢性感染，微生物病原体必须逃离宿主的免疫防御。人类致病性新型隐球菌感染是典型的慢性感染。为了解新生梭菌在免疫功能强的宿主感染后在组织中存活的机制，我们用电镜系统地研究了小鼠肺部感染的过程，在感染的任何时候，巨噬细胞都是主要的吞噬细胞，但中性粒细胞也吞噬酵母。在气管内感染后，肺泡巨噬细胞迅速内化酵母细胞，从2小时到28天的感染时间内，细胞内都有酵母细胞。然而，酵母细胞在细胞内和细胞外空间的比例随感染时间而变化。在感染早期，酵母细胞主要分布在细胞内。24小时后，巨噬细胞向细胞外优势转变，并伴有细胞毒性和破坏。在感染后期，尽管吞噬溶酶体融合，但细胞内的体内持久性与复制、停留在膜结合的吞噬体中、细胞内的多糖积累以及对巨噬细胞的细胞毒性有关。许多带有胞内酵母的吞噬液泡具有不连续的膜。巨噬细胞感染导致细胞具有独特的外观，其特征是大量充满多糖抗原的液泡。在体外使用巨噬细胞样细胞系观察到类似的结果。我们的研究结果表明，新生C.是一种兼性细胞内病原体。此外，我们的观察表明，新生C.在细胞内病原体中占有独特的生态位，因此在吞噬细胞中的生存伴随着细胞内多糖的产生。
To produce chronic infection, microbial pathogens must escape host immune defenses. Infection with the human pathogenic fungus Cryptococcus neoformans is typically chronic. To understand the mechanism by which C. neoformans survives in tissue after the infection of immunocompetent hosts, we systematically studied the course of pulmonary infection in mice by electron microscopy, The macrophage was the primary phagocytic cell at all times of infection, but neutrophils also ingested yeast. Alveolar macrophages rapidly internalized yeast cells after intratracheal infection, and intracellular yeast cells were noted at ail times of infection from 2 h through 28 days. However, the proportion of yeast cells in the intracellular and extracellular spaces varied with the time of infection. Early in infection, yeast cells were found predominantly in the intracellular compartment. A shift toward extracellular predominance occurred by 24 h that was accompanied by macrophage cytotoxicity and disruption. Later in infection, intracellular persistence in vivo was associated with replication, residence in a membrane-bound phagosome, polysaccharide accumulation inside cells, and cytotoxicity to macrophages, despite phagolysosomal fusion. Many phagocytic vacuoles with intracellular yeast had discontinuous membranes. Macrophage infection resulted in cells with a distinctive appearance characterized by large numbers of vacuoles filled with polysaccharide antigen. Similar results were observed in vitro using a macrophage-like cell line. Our results show that C. neoformans is a facultative intracellular pathogen in vivo. Furthermore, our observations suggest that C. neoformans occupies a unique niche among the intracellular pathogens whereby survival in phagocytic cells is accompanied by intracellular polysaccharide production.