An in vitro model of intestinal infection reveals a developmentally regulated transcriptome of Toxoplasma sporozoites and a NF-κB-like signature in infected host cells.
An in vitro model of intestinal infection reveals a developmentally regulated transcriptome of Toxoplasma sporozoites and a NF-κB-like signature in infected host cells.
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DOI：
10.1371/journal.pone.0173018
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Boothroyd JC
中科院分区：
文献类型：
--
作者：
Guiton PS;Sagawa JM;Fritz HM;Boothroyd JC
弓形虫病是一种人畜共患传染病，影响世界上约30%的人口。在最终的猫科宿主中进行有性生殖后，每个含有8个子孢子的弓形虫卵囊被释放到环境中，在那里它们可以继续感染人类和其他温血中间宿主。在这里，我们使用体外模型来评估在这种感染的最早阶段发生的宿主转录组学变化。我们发现，用成熟子孢子感染大鼠肠上皮细胞主要导致与肿瘤坏死因子α（TNFα）通过NF-κB信号转导相关的基因的高表达。此外，我们发现，与它们的生物学相一致，这些成熟的，入侵的子孢子显示先前报道的第10天卵囊和它们的速殖子对应物之间的转录组中间体。因此，这项研究揭示了新的宿主和病原体的因素，可能是一个成功的细胞内生态位的建立子孢子启动感染的关键。
Toxoplasmosis is a zoonotic infection affecting approximately 30% of the world’s human population. After sexual reproduction in the definitive feline host, Toxoplasma oocysts, each containing 8 sporozoites, are shed into the environment where they can go on to infect humans and other warm-blooded intermediate hosts. Here, we use an in vitro model to assess host transcriptomic changes that occur in the earliest stages of such infections. We show that infection of rat intestinal epithelial cells with mature sporozoites primarily results in higher expression of genes associated with Tumor Necrosis Factor alpha (TNFα) signaling via NF-κB. Furthermore, we find that, consistent with their biology, these mature, invaded sporozoites display a transcriptome intermediate between the previously reported day 10 oocysts and that of their tachyzoite counterparts. Thus, this study uncovers novel host and pathogen factors that may be critical for the establishment of a successful intracellular niche following sporozoite-initiated infection.