Division of Medical Parasitology, Department of Microbiology, New York University School of Medicine, New York, New York, United States of America.
PLoS One. 2012;7(8):e43913. doi: 10.1371/journal.pone.0043913. Epub 2012 Aug 31.
Human African trypanosomiasis or sleeping sickness is a vector-borne parasitic disease that has a major impact on human health and welfare in sub-Saharan countries. Based mostly on data from animal models, it is currently thought that trypanosome entry into the brain occurs by initial infection of the choroid plexus and the circumventricular organs followed days to weeks later by entry into the brain parenchyma. However, Trypanosoma brucei bloodstream forms rapidly cross human brain microvascular endothelial cells in vitro and appear to be able to enter the murine brain without inflicting cerebral injury. Using a murine model and intravital brain imaging, we show that bloodstream forms of T. b. brucei and T. b. rhodesiense enter the brain parenchyma within hours, before a significant level of microvascular inflammation is detectable. Extravascular bloodstream forms were viable as indicated by motility and cell division, and remained detectable for at least 3 days post infection suggesting the potential for parasite survival in the brain parenchyma. Vascular inflammation, as reflected by leukocyte recruitment and emigration from cortical microvessels, became apparent only with increasing parasitemia at later stages of the infection, but was not associated with neurological signs. Extravascular trypanosomes were predominantly associated with postcapillary venules suggesting that early brain infection occurs by parasite passage across the neuroimmunological blood brain barrier. Thus, trypanosomes can invade the murine brain parenchyma during the early stages of the disease before meningoencephalitis is fully established. Whether individual trypanosomes can act alone or require the interaction from a quorum of parasites remains to be shown. The significance of these findings for disease development is now testable.
人类非洲锥虫病或昏睡病是一种由寄生虫引起的疾病，主要影响撒哈拉以南国家的人类健康和福利。基于大多数动物模型的数据，目前认为锥虫进入大脑是通过脉络丛和室周器官的初始感染，然后数天至数周后进入大脑实质。然而，布氏锥虫和罗得西亚锥虫的血液形式在体外迅速穿过人脑微血管内皮细胞，似乎能够在不造成脑损伤的情况下进入鼠脑。使用鼠模型和活体脑成像，我们表明，布氏锥虫和罗得西亚锥虫的血液形式在可检测到微血管炎症之前数小时内进入脑实质。如运动和细胞分裂所示，血管外血液形式是有活力的，并且至少在感染后 3 天内仍可检测到，这表明寄生虫在脑实质中存活的潜力。血管炎症，如白细胞从皮质微血管募集和迁移所反映的那样，仅在感染后期随着寄生虫血症的增加而变得明显，但与神经症状无关。血管外锥虫主要与后微静脉相关，表明早期脑感染是通过寄生虫穿过神经免疫血脑屏障的方式发生的。因此，锥虫可以在脑膜脑炎完全建立之前，在疾病的早期阶段侵入鼠脑实质。单个锥虫是否可以单独作用，还是需要一定数量的寄生虫相互作用，还有待证明。这些发现对疾病发展的意义现在是可以检验的。
