Differential transcriptome of human dendritic cells at first contact with Trypanosoma cruzi reveals response to virus as a central unexplored pathway. Differential transcriptome of human dendritic cells at first contact with Trypanosoma cruzi reveals response to virus as a central unexplored pathway

Chagas disease is a notorious public health problem worldwide. However, the pathology is still poorly understood in humans and dendritic cells (DCs) have a determinant role during infection that could help to understand what happens with immune response during the first contact. Here we performed a transcriptomic analysis of the interaction between DCs from three human donors and the infective forms of T. cruzi for 12 h. 468 differentially expressed genes (DEGs) were found in DCs after infection. KEGG and GO enrichment analysis showed that most of DEGs are involved in pathways related to virus infection and intracellular receptors, as NOD and RIG-I -like receptors. Some of these DEGs were validated through RT-qPCR, corroborating the transcriptome data. Cytokine measurement partially corresponded to the transcript levels. In conclusion, this study has revealed the virus response as an unexplored pathway in Chagas disease, which brings new perspectives for this pathology. Overall design: 3 human donors, 2 replicates each, with control and infected samples for each experiment. A total of 12 samples were analyzed.

恰加斯病（Chagas disease）是全球范围内亟待破解的重大公共卫生难题。目前人类对其致病机制仍知之甚少，而树突状细胞（dendritic cells, DCs）在感染过程中发挥决定性作用，或可助力阐明宿主初次接触病原体时的免疫应答机制。本研究针对3名人类供体来源的树突状细胞与克氏锥虫（T. cruzi）感染阶段虫体共培养12小时的相互作用开展转录组分析。感染后，树突状细胞中共筛选得到468个差异表达基因（DEGs）。通过京都基因与基因组百科全书（KEGG）及基因本体论（GO）富集分析发现，绝大多数DEGs富集于病毒感染及胞内受体相关通路，如NOD样受体与RIG-I样受体通路。部分DEGs通过实时定量聚合酶链反应（RT-qPCR）进行了验证，结果与转录组数据一致。细胞因子检测结果与对应转录本水平部分相符。综上，本研究揭示病毒应答通路是恰加斯病研究中尚未被探索的方向，为该疾病的致病机制研究提供了全新视角。整体实验设计：共纳入3名人类供体，每名供体设置2次生物学重复，每次实验均包含对照样本与感染样本，最终共计分析12份样本。