Guiton Pascale S, Sagawa Janelle M, Fritz Heather M, Boothroyd John C
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, United States of America.
Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington, United States of America.
PLoS One. 2017 Mar 31;12(3):e0173018. doi: 10.1371/journal.pone.0173018. eCollection 2017.
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.
弓形虫病是一种人畜共患感染病,影响着全球约30%的人口。在终末宿主猫科动物体内进行有性繁殖后,每个含有8个子孢子的弓形虫卵囊被排放到环境中,在那里它们可以继续感染人类和其他温血中间宿主。在此,我们使用体外模型来评估此类感染早期阶段发生的宿主转录组变化。我们发现,用成熟子孢子感染大鼠肠道上皮细胞主要导致与通过核因子κB(NF-κB)的肿瘤坏死因子α(TNFα)信号传导相关的基因表达上调。此外,我们发现,与其生物学特性一致,这些成熟的、已侵入的子孢子显示出一个转录组,介于先前报道的第10天卵囊和速殖子的转录组之间。因此,本研究揭示了新的宿主和病原体因素,这些因素可能对子孢子引发感染后成功建立细胞内生态位至关重要。