Trypanosoma brucei Invasion and T-Cell Infiltration of the Brain Parenchyma in Experimental Sleeping Sickness: Timing and Correlation with Functional Changes
Trypanosoma brucei Invasion and T-Cell Infiltration of the Brain Parenchyma in Experimental Sleeping Sickness: Timing and Correlation with Functional Changes
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DOI：
10.1371/journal.pntd.0005242
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发表时间：
2016-12-01
影响因子：
3.8
通讯作者：
Bentivoglio, Marina
中科院分区：
文献类型：
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作者：
Laperchia, Claudia;Palomba, Maria;Bentivoglio, Marina
背景布氏锥虫进入脑实质启动第二，脑膜脑炎阶段的人类非洲锥虫病或昏睡病的时间目前有争议，甚至寄生虫入侵的神经系统最近受到质疑。此外，神经功能和疾病阶段之间的关系尚不清楚，尽管重要的诊断和治疗implications.MethodologyUsing慢性布氏锥虫感染的大鼠模型，我们确定了寄生虫和T细胞neurology浸润的时间及其与功能变化的相关性。用锥虫特异性PCR检测寄生虫DNA。体重和睡眠结构的变化代表的睡眠发作快速眼动（SOREM）期间，在人类和实验非洲锥虫报道，进行了监测。寄生虫的存在，以及CD 4+和CD 8 + T-细胞在neurophilis进行了评估，随着时间的推移，在同一动物的大脑中，通过免疫细胞化学和定量analysis. PrincipalfindingsTrypanosomeDNA是存在于大脑中的感染后第6天，并增加了超过15倍的第21天。从第9天开始，在实质中观察到寄生虫和T细胞。在下丘脑和其他脑区观察到寄生虫穿过血管壁。从第7天开始，体重增量降低。SOREM发作开始在大多数情况下感染后早期，寄生虫neuroinvasion.ConclusionThese研究结果表明，随着时间的推移，寄生虫和淋巴细胞穿越血脑屏障后，入侵的neurology的数量和持续时间的增加，并显示神经功能可以在此之前的事件。因此，这些数据挑战了目前的临床和脑脊液疾病分期标准。
BackgroundThe timing of Trypanosoma brucei entry into the brain parenchyma to initiate the second, meningoencephalitic stage of human African trypanosomiasis or sleeping sickness is currently debated and even parasite invasion of the neuropil has been recently questioned. Furthermore, the relationship between neurological features and disease stage are unclear, despite the important diagnostic and therapeutic implications.MethodologyUsing a rat model of chronic Trypanosoma brucei brucei infection we determined the timing of parasite and T-cell neuropil infiltration and its correlation with functional changes. Parasite DNA was detected using trypanosome-specific PCR. Body weight and sleep structure alterations represented by sleep-onset rapid eye movement (SOREM) periods, reported in human and experimental African trypanosomiasis, were monitored. The presence of parasites, as well as CD4+ and CD8+ T-cells in the neuropil was assessed over time in the brain of the same animals by immunocytochemistry and quantitative analyses.Principal findingsTrypanosome DNA was present in the brain at day 6 post-infection and increased more than 15-fold by day 21. Parasites and T-cells were observed in the parenchyma from day 9 onwards. Parasites traversing blood vessel walls were observed in the hypothalamus and other brain regions. Body weight gain was reduced from day 7 onwards. SOREM episodes started in most cases early after infection, with an increase in number and duration after parasite neuroinvasion.ConclusionThese findings demonstrate invasion of the neuropil over time, after an initial interval, by parasites and lymphocytes crossing the blood-brain barrier, and show that neurological features can precede this event. The data thus challenge the current clinical and cerebrospinal fluid criteria of disease staging.