Involvement of human CD44 during Cryptococcus neoformans infection of brain microvascular endothelial cells
Involvement of human CD44 during Cryptococcus neoformans infection of brain microvascular endothelial cells
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DOI：
10.1111/j.1462-5822.2008.01128.x
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发表时间：
2008-06-01
影响因子：
3.4
通讯作者：
Huang, Sheng-He
中科院分区：
文献类型：
--
作者：
Jong, Ambrose;Wu, Chun-Hua;Huang, Sheng-He
致病性酵母菌新型隐球菌会引起毁灭性的隐球菌性脑膜脑炎。我们之前的研究表明，新型隐球菌透明质酸是侵入构成血脑屏障的人脑微血管内皮细胞（HBMEC）所必需的。在本报告中，我们证明了新型隐球菌透明质酸与 HBMEC 上的 CD44 相互作用。基于以下观察，我们的结果表明 HBMEC CD44 是新型隐球菌感染期间的主要受体。首先，抗 CD44 中和抗体治疗能够显着减少新型隐球菌与 HBMEC 的关联。其次，使用 CD44 敲低的 HBMEC 或缺乏新型隐球菌透明质酸的菌株，新型隐球菌关联会受到显着损害。第三，HBMEC 中 CD44 的过度表达增加了它们与新型隐球菌的关联活性。第四，共焦显微图像显示 CD44 在新型隐球菌关联位点及其周围富集。第五，在新型隐球菌和 HBMEC 接触后，CD44 和肌动蛋白的亚群易位至宿主膜筏。我们的结果强调了新型隐球菌透明质酸和宿主 CD44 之间的相互作用以及这些相互作用的动态结果，这可能代表了新型隐球菌在 HBMEC 膜筏上粘附和进入过程中的事件。
Pathogenic yeast Cryptococcus neoformans causes devastating cryptococcal meningoencephalitis. Our previous studies demonstrated that C. neoformans hyaluronic acid was required for invasion into human brain microvascular endothelial cells (HBMEC), which constitute the blood-brain barrier. In this report, we demonstrate that C. neoformans hyaluronic acid interacts with CD44 on HBMEC. Our results suggest that HBMEC CD44 is a primary receptor during C. neoformans infection, based on the following observations. First, anti-CD44 neutralizing antibody treatment was able to significantly reduce C. neoformans association with HBMEC. Second, C. neoformans association was considerably impaired using either CD44-knock-down HBMEC or C. neoformans hyaluronic acid-deficient strains. Third, overexpression of CD44 in HBMEC increased their association activity towards C. neoformans. Fourth, confocal microscopic images showed that CD44 was enriched at and around the C. neoformans association sites. Fifth, upon C. neoformans and HBMEC engagement, a subpopulation of CD44 and actin translocated to the host membrane rafts. Our results highlight the interactions between C. neoformans hyaluronic acid and host CD44 and the dynamic results of these interactions, which may represent events during the adhesion and entry of C. neoformans at HBMEC membrane rafts.