弓形虫是弓形虫病的病原体，弓形虫病影响约三分之一的人口。大多数感染者没有症状，但也可能发生严重病例，例如先天性传播，而感染其他病原体的人（例如艾滋病毒呈阳性的孕妇）的情况可能会加重。然而，尚不清楚其他病原体的感染，例如恰加斯病的病原体克氏锥虫及其蛋白质之一 P21，是否会加重弓形虫感染。从这个意义上说，我们的目的是研究其影响克氏弓形虫和重组 P21 (rP21) 对 BeWo 细胞和人胎盘外植体中弓形虫感染的影响。我们的结果表明，克氏弓形虫感染以及 rP21 增加了 BeWo 细胞中弓形虫的侵袭并降低了细胞内增殖。 rP21 促进的侵袭增加取决于其与 CXCR4 的结合和肌动蛋白细胞骨架聚合，而增殖的减少是由于寄生虫细胞周期中 S/M 期的停滞以及白细胞介素 (IL)- 6 上调和 IL-8 下调。另一方面，在人胎盘绒毛中，rP21可以增加或减少弓形虫增殖，而克氏弓形虫感染则增加弓形虫增殖。这种增加可以通过 IL-4 增加和 IL-6、IL-8、巨噬细胞迁移抑制因子 (MIF) 和肿瘤坏死因子 (TNF)-α 减少诱导抗炎环境来解释。总之，在合并感染的情况下，克氏弓形虫的存在可能有利于弓形虫的先天性传播，凸显了新生儿筛查这两种疾病的重要性，以及以 P21 作为未来治疗靶点的研究的重要性用于治疗恰加斯病，因为它也可能促进弓形虫感染。版权所有 © 2023 de Souza, Teixeira, Fajardo Martínez, Silva, Luz, Lima Júnior, Rosini, dos Santos, de Oliveira, Paschoalino, Barbosa, Alves, Gomes 、达席尔瓦、费罗和巴博萨。

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.Copyright © 2023 de Souza, Teixeira, Fajardo Martínez, Silva, Luz, Lima Júnior, Rosini, dos Santos, de Oliveira, Paschoalino, Barbosa, Alves, Gomes, da Silva, Ferro and Barbosa.