Table_2_Differential Modulation of Mouse Heart Gene Expression by Infection With Two Trypanosoma cruzi Strains: A Transcriptome Analysis.XLSX

The protozoan Trypanosoma cruzi (T. cruzi) is a well-adapted parasite to mammalian hosts and the pathogen of Chagas disease in humans. As both host and T. cruzi are highly genetically diverse, many variables come into play during infection, making disease outcomes difficult to predict. One important challenge in the field of Chagas disease research is determining the main factors leading to parasite establishment in the chronic stage in some organs, mainly the heart and/or digestive system. Our group previously showed that distinct strains of T. cruzi (JG and Col1.7G2) acquired differential tissue distribution in the chronic stage in dually infected BALB/c mice. To investigate changes in the host triggered by the two distinct T. cruzi strains, we assessed the gene expression profiles of BALB/c mouse hearts infected with either JG, Col1.7G2 or an equivalent mixture of both parasites during the initial phase of infection. This study demonstrates the clear differences in modulation of host gene expression by both parasites. Col1.7G2 strongly activated Th1-polarized immune signature genes, whereas JG caused only minor activation of the host immune response. Moreover, JG strongly reduced the expression of genes encoding ribosomal proteins and mitochondrial proteins related to the electron transport chain. Interestingly, the evaluation of gene expression in mice inoculated with a mixture of the parasites produced expression profiles with both up- and downregulated genes, indicating the coexistence of both parasite strains in the heart during the acute phase. This study suggests that different strains of T. cruzi may be distinguished by their efficiency in activating the immune system, modulating host energy metabolism and reactive oxygen species production and decreasing protein synthesis during early infection, which may be crucial for parasite persistence in specific organs.

原生动物克氏锥虫（Trypanosoma cruzi，T. cruzi）是一种高度适应哺乳动物宿主的寄生虫，亦是引发人类恰加斯病的病原体。鉴于宿主与克氏锥虫均具备高度的遗传多样性，感染过程中存在诸多影响因素，导致疾病转归难以预判。恰加斯病研究领域的一项核心挑战，便是明确寄生虫在慢性阶段定植于部分器官（主要为心脏与/或消化系统）的关键驱动因素。本团队此前的研究证实，两种不同的克氏锥虫毒株（JG与Col1.7G2）在双重感染的BALB/c小鼠体内，慢性感染阶段呈现出差异化的组织分布特征。为探究这两种不同克氏锥虫毒株对宿主引发的调控差异，本研究在感染初期，对分别感染JG毒株、Col1.7G2毒株，以及同时感染二者等量混合毒株的BALB/c小鼠心脏组织，开展了基因表达谱分析。本研究证实，两种寄生虫对宿主基因表达的调控存在显著差异：其中Col1.7G2可显著激活Th1极化的免疫特征基因，而JG仅能引发宿主免疫应答的微弱激活。此外，JG可显著下调编码核糖体蛋白及与电子传递链相关的线粒体蛋白的基因表达。值得注意的是，对感染混合毒株小鼠的基因表达检测结果显示，其基因表达谱同时存在上调与下调的基因，表明急性感染阶段心脏内同时存在两种寄生虫毒株。本研究表明，不同克氏锥虫毒株可通过其在感染早期激活免疫系统、调控宿主能量代谢与活性氧生成、降低蛋白质合成的效率加以区分，这一特性或许对于寄生虫在特定器官中的持续定植至关重要。