Schistosoma japonicum soluble egg antigens attenuate invasion in a first trimester human placental trophoblast model.

Schistosoma japonicum soluble egg antigens attenuate invasion in a first trimester human placental trophoblast model.
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DOI:
10.1371/journal.pntd.0002253
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发表时间:
2013
影响因子:
3.8
通讯作者:
Kurtis JD
Kurtis JD
中科院分区:
医学2区
文献类型:
--
作者:
McDonald EA;Friedman JF;Sharma S;Acosta L;Pond-Tor S;Cheng L;White ES;Kurtis JD

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血吸虫病影响了近4000万育龄妇女,并已知会在胎盘中引发促炎信号。我们以前已经证明,来自血吸虫卵的抗原可以特异性地诱导滋养层细胞产生促炎细胞因子;然而,这些抗原对滋养层功能的其他特征的影响尚不清楚,特别是与早期妊娠的胎盘有关的影响。因此,我们试图确定血吸虫抗原对妊娠早期滋养层细胞的关键特征的影响,包括迁移和侵袭。将妊娠早期HTR8/SVneo滋养层细胞与有或无血吸虫病或血吸虫可溶性虫卵抗原(SEA)孕妇的血浆共培养,检测细胞因子、细胞迁移和侵袭反应。HTR8细胞暴露于SEA可导致促炎、抗侵袭的特征,其特征是促炎细胞因子(IL-6、IL-8、MCP-1)和TIMP-1增加。此外,经SEA处理后,这些细胞的体外迁移减少了62%,侵袭力减少了2.7倍。感染日本血吸虫的孕妇血浆中HTR8细胞培养上清液中IL-6和IL-8的升高支持了上述结果。在血吸虫感染期间循环中发现的可溶性虫卵抗原增加了促炎细胞因子的产生,并抑制了妊娠早期HTR8/SVneo滋养层细胞系的迁移和侵袭特性。这是第一次评估血吸虫可溶性虫卵抗原对绒毛外滋养细胞模型行为的影响,并表明妊娠前血吸虫病可能对胎盘和随后的母亲和新生儿的健康产生不利影响。全球任何时候都有大约4000万育龄妇女感染血吸虫。在啮齿动物模型中的多项研究以及在人类中的一些报告表明,血吸虫感染会导致不良的妊娠结局。我们之前已经证明,从血吸虫卵中释放的抗原会导致合体晚期滋养层细胞发生明显的促炎反应。在这里,我们研究了血吸虫卵抗原对妊娠早期滋养层细胞系的影响,滋养层细胞系是一种公认的早期胎盘发育模型。不仅在这个模型系统中重现了促炎反应,而且我们还观察到在暴露于这些抗原后滋养层细胞的迁移和侵袭减少。迁移和侵袭都是早期胎盘发育的关键因素,侵袭不足与妊娠相关疾病,如生长受限和先兆子痫有关。这项研究首次研究了血吸虫抗原对早期胎盘发育的影响,并可能对随后的孕妇和孩子的健康产生影响。
Schistosomiasis affects nearly 40 million women of reproductive age, and is known to elicit a pro-inflammatory signature in the placenta. We have previously shown that antigens from schistosome eggs can elicit pro-inflammatory cytokine production from trophoblast cells specifically; however, the influence of these antigens on other characteristics of trophoblast function, particularly as it pertains to placentation in early gestation, is unknown. We therefore sought to determine the impact of schistosome antigens on key characteristics of first trimester trophoblast cells, including migration and invasion. First trimester HTR8/SVneo trophoblast cells were co-cultured with plasma from pregnant women with and without schistosomiasis or schistosome soluble egg antigens (SEA) and measured cytokine, cellular migration, and invasion responses. Exposure of HTR8 cells to SEA resulted in a pro-inflammatory, anti-invasive signature, characterized by increased pro-inflammatory cytokines (IL-6, IL-8, MCP-1) and TIMP-1. Additionally, these cells displayed 62% decreased migration and 2.7-fold decreased invasion in vitro after treatment with SEA. These results are supported by increased IL-6 and IL-8 in the culture media of HTR8 cells exposed to plasma from Schistosoma japonica infected pregnant women. Soluble egg antigens found in circulation during schistosome infection increase pro-inflammatory cytokine production and inhibit the mobility and invasive characteristics of the first trimester HTR8/SVneo trophoblast cell line. This is the first study to assess the impact of schistosome soluble egg antigens on the behavior of an extravillous trophoblast model and suggests that schistosomiasis in the pre-pregnancy period may adversely impact placentation and the subsequent health of the mother and newborn. Approximately 40 million women of childbearing age suffer from schistosome infection globally at any given time. Multiple studies in rodent models, as well as a few reports in humans, suggest that schistosome infection results in poor pregnancy outcomes. We have previously shown that antigens released from schistosome eggs result in a pronounced pro-inflammatory response in syncytialized third trimester trophoblasts. Herein, we examine the effect of schistosome egg antigens on a first trimester trophoblast cell line, an accepted model for early placental development. Not only is the pro-inflammatory response recapitulated in this model system, but we also observed a decrease in migration and invasion of trophoblast cells after exposure to these antigens. Both migration and invasion are key aspects in early placental development, and inadequate invasion has been implicated in pregnancy-related diseases such as growth restriction and preeclampsia. This study is the first to examine the impact of schistosome antigens on early placental development, and may have implications for the subsequent health of both the pregnancy and the child.
DOI: 10.1093/infdis/jiq099
发表时间: 2011-03-01
影响因子: 6.4
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