Chagas disease, caused by Trypanosoma cruzi, remains a leading cause of infection-driven cardiac pathology. To investigate the impact on gene expression, we used ex vivo imaging to target RNAseq at specific sites of cardiac infection. This integrated workflow allowed parasite foci to be directly linked with host gene expression, revealing  546 upregulated and 158 downregulated genes (FDR < 0.01, |log2FC| = 1).
Chagas disease, caused by Trypanosoma cruzi, remains a leading cause of infection-driven cardiac pathology. Here, we exploited high-resolution X-ray tomography to demonstrate that the heart is a major site of infection during the early acute stage of the disease in mice. To investigate the impact on gene expression, we used ex vivo imaging to target RNAseq at specific sites of cardiac infection. This integrated workflow allowed parasite foci to be directly linked with host gene expression, revealing  546 upregulated and 158 downregulated genes (FDR < 0.01, |log2FC| = 1). GO and KEGG enrichment highlighted interferon-driven immune activation, antigen presentation, complement cascades, and enrichment of Chagas disease and viral myocarditis pathways. Notably, we also uncovered differentially expressed genes, previously not associated with T. cruzi infection, that were linked to immune-metabolic remodelling, translational control, and oxidative-stress regulation. These findings show that T. cruzi rapidly reprograms the cardiac transcriptome early in the infection toward an interferon/antigen-processing state while engaging novel metabolic and stress pathways.
Chagas disease, caused by Trypanosoma cruzi, remains a leading cause of infection-driven cardiac pathology. Here, we exploited high-resolution X-ray tomography to demonstrate that the heart is a major site of infection during the early acute stage of the disease in mice. To investigate the impact on gene expression, we used ex vivo imaging to target RNAseq at specific sites of cardiac infection. This integrated workflow allowed parasite foci to be directly linked with host gene expression, revealing  546 upregulated and 158 downregulated genes (FDR < 0.01, |log2FC| = 1). GO and KEGG enrichment highlighted interferon-driven immune activation, antigen presentation, complement cascades, and enrichment of Chagas disease and viral myocarditis pathways. Notably, we also uncovered differentially expressed genes, previously not associated with T. cruzi infection, that were linked to immune-metabolic remodelling, translational control, and oxidative-stress regulation. These findings show that T. cruzi rapidly reprograms the cardiac transcriptome early in the infection toward an interferon/antigen-processing state while engaging novel metabolic and stress pathways.