■弓形虫是弓形虫病的病原体,一种影响约三分之一人口的疾病。大多数感染者无症状,但是严重的病例可能发生,例如先天性传播,感染其他病原体的个体会加重,如HIV阳性孕妇。然而,未知是否被其他病原体感染,比如克氏锥虫,查加斯病的病因,以及它的一种蛋白质,P21,可加重弓形虫感染。
■在这个意义上,我们旨在研究T.cruzi和重组P21(rP21)对弓形虫感染BeWo细胞和人胎盘外植体的影响。
■我们的结果表明克氏虫感染,与rP21一样,在BeWo细胞中增加弓形虫的侵袭并减少细胞内增殖。rP21促进的侵袭增加依赖于其与CXCR4和肌动蛋白细胞骨架聚合的结合,虽然增殖的减少是由于寄生虫细胞周期的S/M期停滞,以及白细胞介素(IL)-6上调和IL-8下调。另一方面,在人类胎盘绒毛中,rP21可以增加或减少弓形虫增殖,而T.cruzi感染增加弓形虫增殖。这种增加可以通过IL-4的增加和IL-6,IL-8,巨噬细胞迁移抑制因子(MIF)的减少诱导抗炎环境来解释。和肿瘤坏死因子(TNF)-α的产生。
■总而言之,在共感染的情况下,克氏虫的存在可能有利于弓形虫的先天性传播,强调新生儿筛查这两种疾病的重要性,以及将P21作为治疗查加斯病的未来治疗靶点的研究的重要性,因为它也有利于弓形虫感染。
Toxoplasma gondii is the etiologic agent of toxoplasmosis, a disease that affects about one-third of the human population. Most infected individuals are asymptomatic, but severe cases can occur such as in congenital transmission, which can be aggravated in individuals infected with other pathogens, such as HIV-positive pregnant women. However, it is unknown whether infection by other pathogens, such as Trypanosoma cruzi, the etiologic agent of Chagas disease, as well as one of its proteins, P21, could aggravate T. gondii infection.
In this sense, we aimed to investigate the impact of T. cruzi and recombinant P21 (rP21) on T. gondii infection in BeWo cells and human placental explants.
Our results showed that T. cruzi infection, as well as rP21, increases invasion and decreases intracellular proliferation of T. gondii in BeWo cells. The increase in invasion promoted by rP21 is dependent on its binding to CXCR4 and the actin cytoskeleton polymerization, while the decrease in proliferation is due to an arrest in the S/M phase in the parasite cell cycle, as well as interleukin (IL)-6 upregulation and IL-8 downmodulation. On the other hand, in human placental villi, rP21 can either increase or decrease T. gondii proliferation, whereas T. cruzi infection increases T. gondii proliferation. This increase can be explained by the induction of an anti-inflammatory environment through an increase in IL-4 and a decrease in IL-6, IL-8, macrophage migration inhibitory factor (MIF), and tumor necrosis factor (TNF)-α production.
In conclusion, in situations of coinfection, the presence of T. cruzi may favor the congenital transmission of T. gondii, highlighting the importance of neonatal screening for both diseases, as well as the importance of studies with P21 as a future therapeutic target for the treatment of Chagas disease, since it can also favor T. gondii infection.