Activation of chronic toxoplasmosis by transportation stress in a mouse model.
Activation of chronic toxoplasmosis by transportation stress in a mouse model.
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小鼠模型中运输应激激活慢性弓形虫病
DOI：
10.18632/oncotarget.13568
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发表时间：
2016-12-27
期刊：
影响因子：
--
通讯作者：
Zhao J
中科院分区：
文献类型：
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作者：
Shen B;Yuan Y;Cheng J;Pan M;Xia N;Zhang W;Wang Y;Zhou Y;Zhao J
刚地弓形虫是一种专性细胞内寄生虫，感染了世界上25%的人口和大量动物。它可以在中间宿主中以两种形式存在：快速复制的速殖子负责急性感染和缓慢复制的慢殖子负责终身慢性感染。速殖子与慢殖子的相互转化在弓形虫的传播和发病中起着关键作用。然而，控制相互转化的分子机制在很大程度上是未知的。在本研究中，我们建立了小鼠慢性感染模型，研究了运输应激对慢性感染状态的影响。我们的研究结果表明，在模拟运输应激的条件下治疗慢性感染小鼠，降低了几种限制慢性感染的关键细胞因子的水平。在应激处理小鼠的脑囊肿中检测到速殖子特异性基因SAG1（表面抗原1）的表达增加，表明慢殖子被激活并转化为速殖子。利用该模型，我们确定了15种弓形虫蛋白，它们在应激诱导的囊肿再激活过程中具有显著的丰度变化。这些蛋白质为进一步研究慢殖子转化的机制奠定了基础。
Toxoplasma gondiiis an obligate intracellular parasite infecting 25% of the world population and enormous number of animals. It can exist in two forms in intermediate hosts: the fast replicating tachyzoites responsible for acute infection and the slowly replicating bradyzoites responsible for life-long chronic infection. The interconversion between tachyzoites and bradyzoites plays critical roles in the transmission and pathogenesis of T. gondii. However, the molecular mechanisms that govern the interconversion are largely unknown. In this study, we established a chronic infection model in mice and examined the impact of transportation stress on the status of chronic infection. Our results demonstrated that, treating chronically infected mice with conditions mimicking transportation stress reduced the levels of several key cytokines that restrict the infection at chronic stage. Increased expression of the tachyzoite specific gene SAG1 (surface antigen 1) was detected in brain cysts of stress treated mice, indicating activation and conversion of bradyzoites to tachyzoites. Using this model, we identified fifteen toxoplasmic proteins that had significant abundance changes during stress induced cysts reactivation. These proteins serve as a basis for further investigation of the mechanisms governing bradyzoite conversion.