Surfactant Protein D Increases Phagocytosis of Hypocapsular Cryptococcus neoformans by Murine Macrophages and Enhances Fungal Survival
Surfactant Protein D Increases Phagocytosis of Hypocapsular Cryptococcus neoformans by Murine Macrophages and Enhances Fungal Survival
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DOI：
10.1128/iai.00088-09
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发表时间：
2009-07-01
影响因子：
3.1
通讯作者：
Wright, Jo Rae
中科院分区：
文献类型：
--
作者：
Geunes-Boyer, Scarlett;Oliver, Timothy N.;Wright, Jo Rae
新型隐球菌是一种兼性细胞内机会致病菌，是人类真菌性脑膜炎的主要病因。在缺乏保护性细胞免疫应答的情况下，吸入C。新生菌细胞或孢子导致肺部感染。C.新形式细胞产生主要由葡糖醛酸甘露聚糖组成的多糖囊，其构成囊材料的约90%。在肺中，表面活性蛋白A（SP-A）和SP-D通过促进吞噬细胞聚集、摄取和杀死许多微生物而有助于免疫防御。我们推测SP-D在C.通过结合并增强酵母的吞噬作用来抑制新生儿的发病。在此，评估了SP-D与野生型包囊化菌株H99和cap 59 Delta突变体下包囊菌株结合并促进其吞噬作用和存活的能力。SP-D与cap 59 Delta突变体细胞的结合比与野生型细胞的结合高约6倍。SP-D在体外将cap 59 δ细胞的吞噬作用增强约四倍。为了研究体内SP-D结合，用Alexa Fluor 488标记的cap 59 Delta或H99细胞鼻内接种SP-D-/-小鼠。通过共聚焦显微镜观察，吞噬的C.观察到野生型小鼠中的新生儿细胞多于SP-D-/-小鼠，这与体外数据一致。有趣的是，SP-D保护C。在体外，通过使用CFU测定分析真菌活力来证明新生菌细胞针对巨噬细胞介导的防御机制。这些发现为C.新型原虫破坏了涉及表面活性剂的宿主防御机制，建立了一种新的毒力模式，可用于治疗。
Cryptococcus neoformans is a facultative intracellular opportunistic pathogen and the leading cause of fungal meningitis in humans. In the absence of a protective cellular immune response, the inhalation of C. neoformans cells or spores results in pulmonary infection. C. neoformans cells produce a polysaccharide capsule composed predominantly of glucuronoxylomannan, which constitutes approximately 90% of the capsular material. In the lungs, surfactant protein A (SP-A) and SP-D contribute to immune defense by facilitating the aggregation, uptake, and killing of many microorganisms by phagocytic cells. We hypothesized that SP-D plays a role in C. neoformans pathogenesis by binding to and enhancing the phagocytosis of the yeast. Here, the abilities of SP-D to bind to and facilitate the phagocytosis and survival of the wild-type encapsulated strain H99 and the cap59 Delta mutant hypocapsular strain are assessed. SP-D binding to cap59 Delta mutant cells was approximately sixfold greater than binding to wild-type cells. SP-D enhanced the phagocytosis of cap59 Delta cells by approximately fourfold in vitro. To investigate SP-D binding in vivo, SP-D-/- mice were intranasally inoculated with Alexa Fluor 488-labeled cap59 Delta or H99 cells. By confocal microscopy, a greater number of phagocytosed C. neoformans cells in wild-type mice than in SP-D-/- mice was observed, consistent with in vitro data. Interestingly, SP-D protected C. neoformans cells against macrophage-mediated defense mechanisms in vitro, as demonstrated by an analysis of fungal viability using a CFU assay. These findings provide evidence that C. neoformans subverts host defense mechanisms involving surfactant, establishing a novel virulence paradigm that may be targeted for therapy.