...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Infection and immunity >Evidence of a Role for Monocytes in Dissemination and Brain Invasion by Cryptococcus neoformans
【24h】

Evidence of a Role for Monocytes in Dissemination and Brain Invasion by Cryptococcus neoformans

机译：单核细胞在新型隐球菌的传播和脑侵袭中作用的证据

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The pathogenesis of cryptococcosis, including the events leading to the production of meningoencephalitis, is still largely unknown. Evidence of a transcellular passage of Cryptococcus neoformans across the blood-brain barrier (BBB) and subsequent BBB disruption exists, but the paracellular passage of free yeasts and the role of monocytes in yeast dissemination and brain invasion (Trojan horse method) remain uncertain. We used our model of disseminated cryptococcosis, in which crossing of the BBB starts 6 h after intravenous inoculation, to study paracellular passage of the BBB. We prepared bone marrow-derived monocytes (BMDM) infected in vitro with C. neoformans (BMDM yeasts) and free yeasts and measured fungal loads in tissues. (i) Spleen and lung CFU were >2-fold higher in mice treated with BMDM yeasts than in those treated with free yeasts for 1 and 24 h (P < 0.05), while brain CFU were increased (3.9 times) only at 24 h (P < 0.05). (ii) By comparing the kinetics of brain invasion in na?ve mice and in mice with preestablished cryptococcosis, we found that CFU were lower in the latter case, except at 6 h, when CFU from mice inoculated with BMDM yeasts were comparable to those measured in na?ve mice and 2.5-fold higher than those in mice with preestablished cryptococcosis who were inoculated with free yeasts. (iii) Late phagocyte depletion obtained by clodronate injection reduced disease severity and lowered the fungal burden by 40% in all organs studied. These results provide evidence for Trojan horse crossing of the BBB by C. neoformans, together with mechanisms involving free yeasts, and overall for a role of phagocytes in fungal dissemination.
机译：隐球菌病的发病机制，包括导致脑膜脑炎发生的事件，仍是未知之数。存在新隐球菌跨血脑屏障（BBB）的跨细胞传代和随后的BBB破坏的证据，但是游离酵母的旁细胞传代以及单核细胞在酵母传播和脑侵袭中的作用（Trojan马法）仍不确定。我们使用了传播性隐球菌的模型，在该模型中，静脉内接种后6小时开始BBB的穿越，以研究BBB的旁细胞传代。我们准备了体外用 C感染的骨髓衍生单核细胞（BMDM）。 Neoformans （BMDM酵母）和游离酵母，并测量组织中的真菌含量。 （i）用BMDM酵母处理的小鼠脾脏和肺CFU分别比用游离酵母处理的小鼠1和24 h高<2倍（ P <0.05），而脑CFU升高（ 3.9次）仅在24小时（ P <0.05）。 （ii）通过比较幼稚小鼠和预先建立的隐球菌病小鼠的脑部侵袭动力学，我们发现后者的CFU较低，除了在6 h时，接种BMDM酵母的小鼠的CFU与那些小鼠的CFU相当。在幼稚的小鼠中测得的浓度比未接种酵母的预先建立的隐球菌病小鼠高2.5倍。 （iii）在所有研究的器官中，通过氯膦酸盐注射获得的晚期吞噬细胞耗竭降低了疾病的严重程度，并将真菌负担降低了40％。这些结果为 C穿越BBB的特洛伊木马提供了证据。新菌，以及涉及游离酵母的机制，以及吞噬细胞在真菌传播中的总体作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号