Early invasion of brain parenchyma by African trypanosomes.
Early invasion of brain parenchyma by African trypanosomes.
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DOI：
10.1371/journal.pone.0043913
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Grab DJ
中科院分区：
文献类型：
--
作者：
Frevert U;Movila A;Nikolskaia OV;Raper J;Mackey ZB;Abdulla M;McKerrow J;Grab DJ
非洲人类锥虫病或昏睡病是一种媒介传播的寄生虫病，对撒哈拉以南国家的人类健康和福利有重大影响。主要基于动物模型的数据，目前认为锥虫进入大脑是通过脉络丛最初的感染和脑室周围器官的感染，几天到几周后进入脑实质。然而，布鲁氏锥虫的血流在体外迅速穿过人脑微血管内皮细胞，似乎能够进入小鼠的大脑而不会造成脑损伤。使用小鼠模型和活体脑成像，我们发现布鲁氏结核杆菌和罗氏结核杆菌的血流形式在几个小时内进入脑实质，在显著水平的微血管炎症被检测到之前。根据运动和细胞分裂情况，血管外血流形式是可行的，并在感染后至少3天内仍可检测到，这表明寄生虫在脑实质中存活的可能性。血管炎症，如白细胞从皮质微血管聚集和迁移所反映的，只有在感染后期寄生虫血症增加时才明显，但与神经体征无关。血管外锥虫主要与毛细血管后小静脉有关，这表明早期脑感染是通过寄生虫穿越神经免疫血脑屏障而发生的。因此，在脑膜脑炎完全确诊之前，锥虫可以在疾病的早期阶段入侵小鼠的脑实质。单独的锥虫是否可以单独行动，或者需要大量寄生虫的相互作用，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。
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.
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影响因子：
6.7
作者：
Baer K;Klotz C;Kappe SH;Schnieder T;Frevert U
通讯作者：
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影响因子：
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影响因子：
3.8
作者：
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通讯作者：
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影响因子：
3.8
作者：
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