Medina Lisvaneth, Castillo Christian, Liempi Ana, Guerrero-Muñoz Jesús, Rojas-Pirela Maura, Maya Juan Diego, Prieto Humberto, Kemmerling Ulrike
Programa de Anatomía y Biología del Desarrollo, Facultad de Medicina, Instituto de Ciencias Biomédicas, Universidad de Chile, Santiago, Chile.
Instituto de Biología, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile.
Front Immunol. 2020 Nov 6;11:595250. doi: 10.3389/fimmu.2020.595250. eCollection 2020.
and are two parasites than can be transmitted from mother to child through the placenta. However, congenital transmission rates are low for and high for . Infection success or failure depends on complex parasite-host interactions in which parasites can alter host gene expression by modulating non-coding RNAs such as miRNAs. As of yet, there are no reports on altered miRNA expression in placental tissue in response to either parasite. Therefore, we infected human placental explants by cultivation with either or for 2 h. We then analyzed the miRNA expression profiles of both types of infected tissue by miRNA sequencing and quantitative PCR, sequence-based miRNA target prediction, pathway functional enrichment, and upstream regulator analysis of differentially expressed genes targeted by differentially expressed miRNAs. Both parasites induced specific miRNA profiles. GO analysis revealed that the predicted targets of the differentially expressed miRNAs regulated different cellular processes involved in development and immunity, and most of the identified KEGG pathways were related to chronic diseases and infection. Considering that the differentially expressed miRNAs identified here modulated crucial host cellular targets that participate in determining the success of infection, these miRNAs might explain the differing congenital transmission rates between the two parasites. Molecules of the different pathways that are regulated by miRNAs and modulated during infection, as well as the miRNAs themselves, may be potential targets for the therapeutic control of either congenital Chagas disease or toxoplasmosis.
[某种寄生虫1]和[某种寄生虫2]是两种可通过胎盘由母亲传播给孩子的寄生虫。然而，[某种寄生虫1]的先天性传播率较低，而[某种寄生虫2]的先天性传播率较高。感染的成功或失败取决于复杂的寄生虫-宿主相互作用，在这种相互作用中，寄生虫可通过调节非编码RNA（如miRNA）来改变宿主基因表达。截至目前，尚无关于胎盘组织中因任何一种寄生虫而导致miRNA表达改变的报道。因此，我们通过用[某种寄生虫1]或[某种寄生虫2]培养2小时来感染人胎盘外植体。然后，我们通过miRNA测序和定量PCR、基于序列的miRNA靶标预测、通路功能富集以及对差异表达miRNA靶向的差异表达基因进行上游调节因子分析，来分析两种感染组织的miRNA表达谱。两种寄生虫均诱导了特定的miRNA谱。基因本体（GO）分析显示，差异表达miRNA的预测靶标调节了参与发育和免疫的不同细胞过程，并且鉴定出的大多数京都基因与基因组百科全书（KEGG）通路都与慢性疾病和感染有关。鉴于此处鉴定出的差异表达miRNA调节了参与确定感染成功与否的关键宿主细胞靶标，这些miRNA可能解释了两种寄生虫先天性传播率的差异。在感染期间由miRNA调节和调控的不同通路的分子，以及miRNA本身，可能是先天性恰加斯病或弓形虫病治疗控制的潜在靶点。
