Global transcriptional responses to T. cruzi infection: type I IFN response
Interaction with intracellular pathogens produces characteristic transcriptional signatures in host cells.71 Vaena de Avalos et al.72 dissected the transcriptional response of human fibroblast to T. cruzi infection using microarray technology and showed that the parasite elicits very little transcriptional changes early in the intracellular infection. However, at 24 h postinfection, the transcriptional signature shows very clear upregulation of ISGs due to infected IFN-в production by the infected fibroblasts. Importantly, this transcriptional signature characterized by ISGs was not present in similar studies with other intracellular pathogens, including T. gondii3 and Salmonella.74 Additional studies characterized transcriptional responses to T. cruzi infection in three different primary human cell types relevant to the infection in vivo: fibroblasts, smooth muscle cells, and endothelial cells, reporting a shared ISGs induction signature that was driven by soluble/secreted cytokines as demonstrated using transwell plates.75 When analyzing the gene- ontology functions to which the commonly upregulated genes belonged to, “IFN signaling” and “antigen presentation” emerged as the top signaling pathways induced in all three cell types, consistent with strong increase in IFNe gene
transcription. In conjunction, these studies demonstrate that type I IFN drives the early transcriptional response to T. cruzi infection.