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Ex vivo infection of canine and ovine placental explants with Trypanosoma cruzi and Toxoplasma gondii: differential activation of NF kappa B signaling pathways
Acta Tropica ( IF 2.1 ) Pub Date : 2020-11-24 , DOI: 10.1016/j.actatropica.2020.105766
Ana Liempi , Christian Castillo , Lisvaneth Medina , Maura Rojas-Pirela , Sebastian Araneda , Juan Diego Maya , Victor H. Parraguez , Ulrike Kemmerling

Chagas disease and toxoplasmosis, caused by Trypanosoma cruzi and Toxoplasma gondii, respectively, are important zoonotic diseases affecting humans, companion animals, and livestock, responsible for major health and economic burden. Both parasites can be transmitted vertically in different mammalian species through the placenta. Of note, the transmission rate of T. cruzi is low in dogs, whereas that of T. gondii is high in sheep. The probability of congenital infection depends on complex parasite-host interactions; parasite factors, maternal and fetal immune responses and placental responses all have a role in infection establishment. Since the innate immune response is regulated, at least partially, by NF-κB signaling pathways, our main objective was to determine the effect of ex vivo infection of canine (CPE) and ovine (OPE) placental explants with both parasites, on the activation of canonical and non-canonical NF-κB pathways and its relation to infection. Here, we show that T. cruzi activates both the NF-κB canonical and non-canonical pathways in CPE and OPE, unlike T. gondii, that activates only the canonical pathway in CPE and has no effect on the non-canonical pathway in both explants. Moreover, the inhibition of either or both NF-κB pathways increases the DNA load of T. cruzi in both explants, modulates, on the other hand, T. gondii infection in a differential fashion. Overall, we conclude that the differential modulation of the NF-κB pathways by both pathogens in placental explants might explain, at least partially, the differences in transmission rates of T. cruzi and T. gondii in different mammalian species.



中文翻译:

离体狗的感染和羊胎盘外植体与克氏锥虫弓形虫:NF的差动活化卡帕乙信号传导途径

克鲁格氏锥虫弓形虫分别引起的南美锥虫病和弓形虫病是影响人,伴侣动物和牲畜的重要人畜共患病,造成重大的健康和经济负担。两种寄生虫均可通过胎盘在不同的哺乳动物中垂直传播。值得注意的是,犬的克鲁维氏菌的传播率较低,而弓形虫的传播率较低羊高。先天性感染的可能性取决于复杂的寄生虫-宿主相互作用。寄生虫因素,母体和胎儿的免疫反应以及胎盘反应均在感染建立中起作用。由于先天免疫反应至少部分受NF-κB信号传导通路的调节,因此我们的主要目标是确定两种寄生虫对犬(CPE)和绵羊(OPE)胎盘外植体的体外感染对激活的影响和非典型的NF-κB通路的变化及其与感染的关系。在这里,我们表明,与弓形虫不同,克鲁斯氏杆菌同时激活CPE和OPE中的NF-κB规范和非规范途径,仅激活CPE中的经典途径,而对两种外植体中的非经典途径均无影响。此外,对任一或两个NF-κB途径的抑制都会增加两个外植体中克氏锥虫的DNA负载,另一方面以不同的方式调节弓形虫的感染。总的来说,我们得出的结论是,两种病原体在胎盘外植体中对NF-κB通路的差异调节可能至少部分解释了不同哺乳动物物种中克鲁氏锥虫弓形虫传播速率的差异。

更新日期:2020-12-01
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