Cryptococcus neoformans-derived microvesicles enhance the pathogenesis of fungal brain infection.
Cryptococcus neoformans-derived microvesicles enhance the pathogenesis of fungal brain infection.
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DOI：
10.1371/journal.pone.0048570
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Jong A
中科院分区：
文献类型：
--
作者：
Huang SH;Wu CH;Chang YC;Kwon-Chung KJ;Brown RJ;Jong A
隐球菌性脑膜脑炎是中枢神经系统最常见的真菌疾病。新型隐球菌侵入大脑的机制在很大程度上是未知的。在这项研究中，我们发现C. neoformans衍生的微泡（cnmv）可以增强C. neoformans对血脑屏障（BBB）的穿越。免疫荧光成像显示，cnmv可以与脑血脑屏障成分人脑微血管内皮细胞（HBMECs）融合。这种活性可能是由于cnmv激活HBMEC膜筏并诱导细胞融合活性的能力。在被感染的大脑和脑脊液中发现，cnmv也增强了脑新生C.感染。在受感染的小鼠大脑中，cnmv分布在新生C.诱导的囊性病变内部和周围。囊性病变周围可见胶质原纤维酸性蛋白阳性星形胶质细胞，与14-3-3-GFP（14-3-3-绿色荧光蛋白融合）信号重叠。在CnMV染色密度高的区域可以观察到实质性的变化。这是首次证明新隐球菌衍生的微泡可以促进隐球菌穿过血脑屏障并在新隐球菌感染的大脑病变部位积聚。本研究结果提示cnmv在隐球菌性脑膜脑炎发病中起重要作用。
Cryptococcal meningoencephalitis is the most common fungal disease in the central nervous system. The mechanisms by which Cryptococcus neoformans invades the brain are largely unknown. In this study, we found that C. neoformans-derived microvesicles (CnMVs) can enhance the traversal of the blood-brain barrier (BBB) by C. neoformans in vitro. The immunofluorescence imaging demonstrates that CnMVs can fuse with human brain microvascular endothelial cells (HBMECs), the constituents of the BBB. This activity is presumably due to the ability of the CnMVs to activate HBMEC membrane rafts and induce cell fusogenic activity. CnMVs also enhanced C. neoformans infection of the brain, found in both infected brains and cerebrospinal fluid. In infected mouse brains, CnMVs are distributed inside and around C. neoformans-induced cystic lesions. GFAP (glial fibrillary acidic protein)-positive astrocytes were found surrounding the cystic lesions, overlapping with the 14-3-3-GFP (14-3-3-green fluorescence protein fusion) signals. Substantial changes could be observed in areas that have a high density of CnMV staining. This is the first demonstration that C. neoformans-derived microvesicles can facilitate cryptococcal traversal across the BBB and accumulate at lesion sites of C. neoformans-infected brains. Results of this study suggested that CnMVs play an important role in the pathogenesis of cryptococcal meningoencephalitis.
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影响因子：
4
作者：
Silverman, Judith Maxwell;Clos, Joachim;Reiner, Neil E.
通讯作者：
Reiner, Neil E.
影响因子：
5.1
作者：
Kang, Wenfei;Hebert, Jean M.
通讯作者：
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影响因子：
3.4
作者：
Jong, Ambrose;Wu, Chun-Hua;Huang, Sheng-He
通讯作者：
Huang, Sheng-He
影响因子：
3.4
作者：
Jong, Ambrose;Wu, Chun-Hua;Huang, Sheng-He
通讯作者：
Huang, Sheng-He
DOI：
10.1073/pnas.0308413101
发表时间：
2004-06-29
影响因子：
11.1
作者：
Fevrier, B;Vilette, D;Raposo, G
通讯作者：
Raposo, G