Dual RNA-Seq reveals strain-specific transcriptional adaptations of Trypanosoma cruzi in host cells infected with isolates from acute and chronic cases

Chagas disease, caused by the protozoan Trypanosoma cruzi, remains a major public health issue, particularly in Latin America, and is traditionally transmitted by triatomine bugs. Chagas disease progresses through two phases: an acute phase characterized by high parasitemia and a chronic phase, which may remain asymptomatic or develop into severe complications. This study utilized dual-RNAseq technology to analyze gene expression in mice fibroblast host cells infected with the strain JJ21 isolated from an acute Chagas disease case of presumptive oral transmission, comparing it with the MG strain isolated from a chronic Chagas disease human case. The results revealed that JJ21 exhibits a distinct transcriptional profile, marked by the up-regulation of immune evasion and stress response genes, suggesting specific adjustments to meet the demands of the acute phase. At 24 h post-infection, host cells exhibited increased expression of genes related to immune recognition, cargo receptor activity, and pro-inflammatory responses, indicating a robust initial defensive reaction. By 72 h, the host response shifted towards stress management and antioxidant activity, reflecting efforts to handle prolonged infection. Comparative analysis with the MG strain revealed significant differences: JJ21 showed notable up-regulation of mucin and down-regulation of dynein, indicating unique strategies for evading immune responses and altering intracellular interactions. The heightened expression of virulence factors such as trans-sialidases (Ts) and GP63 proteins in JJ21 supports this hypothesis. In conclusion, this study reveals how the JJ21 strain's unique pro-inflammatory response and adaptive strategies enhance our understanding of strain specific responses during the Chagas disease. These insights are crucial for developing targeted interventions and vaccines to more effectively manage the disease and its global impact.