Table_2_Trypanosoma cruzi and Toxoplasma gondii Induce a Differential MicroRNA Profile in Human Placental Explants.xlsx

Trypanosoma cruzi and Toxoplasma gondii are two parasites than can be transmitted from mother to child through the placenta. However, congenital transmission rates are low for T. cruzi and high for T. gondii. 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 ex vivo by cultivation with either T. cruzi or T. gondii 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 in silico 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.

克氏锥虫和弓形虫是两种可以通过胎盘从母亲传播给儿童的寄生虫。然而，克氏锥虫的先天性传播率较低，而弓形虫则较高。感染的成功与否取决于复杂的寄生虫-宿主相互作用，在这些相互作用中，寄生虫可以通过调节诸如miRNA等非编码RNA来改变宿主基因的表达。截至目前，尚未有关于对任何一种寄生虫产生反应的胎盘组织中miRNA表达改变的报道。因此，我们通过在体外培养2小时，使用克氏锥虫或弓形虫感染人胎盘组织，然后通过miRNA测序和定量PCR分析两种感染组织的miRNA表达谱，基于序列的miRNA靶标预测，差异表达miRNA靶向基因的上游调控分析，以及差异表达miRNA靶向的不同基因的功能通路富集分析。两种寄生虫均诱导了特定的miRNA谱。GO分析揭示了不同ially expressed miRNAs的模拟靶标调控了参与发育和免疫的多种细胞过程，并且大多数确定的KEGG通路与慢性疾病和感染相关。鉴于此处识别的差异表达miRNAs调节了参与决定感染成功与否的关键宿主细胞靶标，这些miRNAs可能解释了两种寄生虫之间先天性传播率的差异。受miRNA调节并在感染过程中被调节的不同通路中的分子，以及miRNA本身，可能成为治疗控制先天性查加斯病或弓形虫病的潜在靶点。