Mogk Stefan, Meiwes Andreas, Shtopel Swetlana, Schraermeyer Ulrich, Lazarus Michael, Kubata Bruno, Wolburg Hartwig, Duszenko Michael
Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany.
Institute of Ophthalmology, University of Tübingen, Tübingen, Germany.
PLoS One. 2014 Mar 11;9(3):e91372. doi: 10.1371/journal.pone.0091372. eCollection 2014.
It is textbook knowledge that human infective forms of Trypanosoma brucei, the causative agent of sleeping sickness, enter the brain across the blood-brain barrier after an initial phase of weeks (rhodesiense) or months (gambiense) in blood. Based on our results using an animal model, both statements seem questionable. As we and others have shown, the first infection relevant crossing of the blood brain border occurs via the choroid plexus, i.e. via the blood-CSF barrier. In addition, counting trypanosomes in blood-free CSF obtained by an atlanto-occipital access revealed a cyclical infection in CSF that was directly correlated to the trypanosome density in blood infection. We also obtained conclusive evidence of organ infiltration, since parasites were detected in tissues outside the blood vessels in heart, spleen, liver, eye, testis, epididymis, and especially between the cell layers of the pia mater including the Virchow-Robin space. Interestingly, in all organs except pia mater, heart and testis, trypanosomes showed either a more or less degraded appearance of cell integrity by loss of the surface coat (VSG), loss of the microtubular cytoskeleton and loss of the intracellular content, or where taken up by phagocytes and degraded intracellularly within lysosomes. This is also true for trypanosomes placed intrathecally into the brain parenchyma using a stereotactic device. We propose a different model of brain infection that is in accordance with our observations and with well-established facts about the development of sleeping sickness.
昏睡病的病原体布氏锥虫的人类感染形式，在血液中经过数周（罗德西亚锥虫）或数月（冈比亚锥虫）的初始阶段后，穿过血脑屏障进入大脑，这是教科书上的知识。基于我们使用动物模型得出的结果，这两种说法似乎都值得怀疑。正如我们和其他人所表明的，与感染相关的首次血脑边界穿越是通过脉络丛，即通过血脑脊液屏障发生的。此外，通过枕骨大孔穿刺获取的无血脑脊液中锥虫计数显示，脑脊液中的周期性感染与血液感染中的锥虫密度直接相关。我们还获得了器官浸润的确凿证据，因为在心脏、脾脏、肝脏、眼睛、睾丸、附睾的血管外组织中检测到了寄生虫，尤其是在软脑膜的细胞层之间，包括维尔肖-罗宾间隙。有趣的是，在除软脑膜、心脏和睾丸之外的所有器官中，锥虫要么因表面糖蛋白（VSG）丢失、微管细胞骨架丢失和细胞内物质丢失而呈现出或多或少细胞完整性退化的外观，要么被吞噬细胞摄取并在溶酶体内进行细胞内降解。对于使用立体定位装置鞘内注射到脑实质中的锥虫也是如此。我们提出了一种不同的脑部感染模型，该模型与我们的观察结果以及关于昏睡病发展的既定事实相符。
