Programa de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Programa de Farmacología Molecular y Clínica, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Acta Trop. 2019 Nov;199:105153. doi: 10.1016/j.actatropica.2019.105153. Epub 2019 Aug 27.
Trypanosoma cruzi (T. cruzi) and Toxoplasma gondii (T. gondii) are the causative agents of Chagas disease and Toxoplasmosis. T. cruzi and T. gondii present, respectively, low and high congenital transmission rates and induce a distinctive cytokine/chemokine profile in ex vivo infected human placental explants (HPE). 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 with both parasites on the activation of canonical and non-canonical NF-κB pathways and its relation to parasite infection. T. cruzi activates both, the canonical and non-canonical pathways of NF-κB, unlike T. gondii, which has no effect on the canonical pathway and inhibits the non-canonical pathway. The inhibition of both pathways of NF-κB increases the DNA load of T. cruzi and T. gondii in HPE. Therefore, the differential modulation of NF-κB signal transduction pathways by both parasites might explain, at least partially, the low and high congenital transmission rates of T. cruzi and T. gondii.
克氏锥虫(T. cruzi)和刚地弓形虫(T. gondii)分别是恰加斯病和弓形体病的病原体。T. cruzi 和 T. gondii 的先天性传播率分别较低和较高,并在体外感染的人胎盘绒毛外植体(HPE)中诱导独特的细胞因子/趋化因子谱。由于先天免疫反应至少部分受到 NF-κB 信号通路的调节,我们的主要目标是确定两种寄生虫体外感染对经典和非经典 NF-κB 通路激活的影响及其与寄生虫感染的关系。与 T. gondii 不同,T. cruzi 激活了经典和非经典的 NF-κB 通路,而 T. gondii 对经典通路没有影响,并且抑制了非经典通路。NF-κB 两条通路的抑制都会增加 HPE 中 T. cruzi 和 T. gondii 的 DNA 载量。因此,两种寄生虫对 NF-κB 信号转导通路的不同调节至少部分解释了 T. cruzi 和 T. gondii 的低和高先天性传播率。