Toxoplasma co-opts host gene expression by injection of a polymorphic kinase homologue
Toxoplasma co-opts host gene expression by injection of a polymorphic kinase homologue
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DOI：
10.1038/nature05395
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发表时间：
2007-01-18
期刊：
影响因子：
64.8
通讯作者：
Boothroyd, J. C.
中科院分区：
文献类型：
--
作者：
Saeij, J. P. J.;Coller, S.;Boothroyd, J. C.
弓形虫是尖端复合门的一种专性细胞内寄生虫，可在免疫系统不成熟或受抑制的人类身上引起严重疾病。弓形虫感染的结果高度依赖于菌株类型，其许多体外生长特性也是如此[1]。在这里，我们使用II型和III型品系之间的遗传杂交来表明，宿主细胞转录调控中的菌株特异性差异是由一种假定的蛋白激酶ROP16介导的。当被寄生虫入侵时，这种多态蛋白从称为棒状病毒的顶端细胞器中释放出来，并注入宿主细胞，在那里它最终影响信号转导和转录激活因子(STAT)信号通路的激活，从而对关键宿主细胞因子IL(IL)-12产生下游影响。我们的发现为细胞内真核病原体如何与宿主相互作用提供了一种新的机制，并揭示了不同弓形虫谱系如何进化以利用这种相互作用的重要差异。
Toxoplasma gondii, an obligate intracellular parasite of the phylum Apicomplexa, can cause severe disease in humans with an immature or suppressed immune system. The outcome of Toxoplasma infection is highly dependent on the strain type, as are many of its in vitro growth properties(1). Here we use genetic crosses between type II and III lines to show that strain-specific differences in the modulation of host cell transcription are mediated by a putative protein kinase, ROP16. Upon invasion by the parasite, this polymorphic protein is released from the apical organelles known as rhoptries and injected into the host cell, where it ultimately affects the activation of signal transducer and activator of transcription ( STAT) signalling pathways and consequent downstream effects on a key host cytokine, interleukin (IL)-12. Our findings provide a new mechanism for how an intracellular eukaryotic pathogen can interact with its host and reveal important differences in how different Toxoplasma lineages have evolved to exploit this interaction.