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ERK1/2 磷酸化和 IL-6 产生参与三种类型的人(细胞合体/合体外)滋养层细胞对弓形虫感染的易感性差异。

ERK1/2 phosphorylation and IL-6 production are involved in the differential susceptibility to Toxoplasma gondii infection in three types of human (cyto/ syncytio/ extravillous) trophoblast cells.

机构信息

Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Sciences, Federal University of Uberlândia, 38405-320, Uberlândia, MG, Brazil.

Laboratory of Cell Biology, Institute of Biological and Natural Sciences, Federal University of Triângulo Mineiro, 38025-180, Uberaba, MG, Brazil.

出版信息

Tissue Cell. 2021 Oct;72:101544. doi: 10.1016/j.tice.2021.101544. Epub 2021 Apr 15.

Abstract

During pregnancy, Toxoplasma gondii can triggers serious manifestations and potentially affect the fetal development. In this scenario, differences in susceptibility of trophoblast cells to T. gondii infection might be evaluated in order to establish new therapeutic approaches capable of interfering in the control of fetal infection by T. gondii. This study aimed to evaluate the susceptibility of cytotrophoblast, syncytiotrophoblast and extravillous trophoblast cells to T. gondii infection. Our data demonstrate that HTR-8/SVneo cells (extravillous trophoblast cells) present higher susceptibility to T. gondii infection when compared to syncytiotrophoblast and cytotrophoblast cells, whereas syncytiotrophoblast was the cell type more resistant to the parasite infection. Also, cytotrophoblast and syncytiotrophoblast cells produced significantly more IL-6 than HTR-8/SVneo cells. On the other hand, HTR-8/SVneo cells showed higher ERK1/2 phosphorylation than cytotrophoblast and syncytiotrophoblast cells. ERK1/2 inhibition reduced T. gondii infection and increased IL-6 production in HTR-8/SVneo cells. Thus, it is plausible to conclude that the greater susceptibility of HTR-8/SVneo cells to infection by T. gondii is related to a higher ERK1/2 phosphorylation and lower levels of IL-6 in these cells compared to other cells, suggesting that these mediators may be important to favor the parasite infection in this type of trophoblastic population.

摘要

在怀孕期间,弓形虫可能会引发严重的表现,并可能影响胎儿的发育。在这种情况下,可以评估滋养细胞对弓形虫感染的易感性差异,以便建立新的治疗方法,能够干预弓形虫对胎儿的感染控制。本研究旨在评估滋养层细胞、合体滋养层细胞和绒毛外滋养层细胞对弓形虫感染的易感性。我们的数据表明,与合体滋养层细胞和滋养层细胞相比,HTR-8/SVneo 细胞(绒毛外滋养层细胞)对弓形虫感染的易感性更高,而合体滋养层细胞是对寄生虫感染最具抵抗力的细胞类型。此外,滋养层细胞和合体滋养层细胞产生的 IL-6 明显多于 HTR-8/SVneo 细胞。另一方面,HTR-8/SVneo 细胞的 ERK1/2 磷酸化水平高于滋养层细胞和合体滋养层细胞。ERK1/2 抑制减少了 HTR-8/SVneo 细胞中的弓形虫感染并增加了 IL-6 的产生。因此,可以得出结论,与其他细胞相比,HTR-8/SVneo 细胞对弓形虫感染的更高易感性与这些细胞中更高的 ERK1/2 磷酸化和更低的 IL-6 水平有关,这表明这些介质可能对有利于这种滋养层细胞群中的寄生虫感染很重要。

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