Transcriptomic changes and immune modulation associated with antiparasitic treatment in chronic Trypanosoma cruzi infection.

Abstract

Chagas disease is a neglected tropical infection that affects over 6 million people worldwide. This study explores transcriptomic changes in <em>T. cruzi</em>-infected subjects before and after receiving treatment. Using total RNA sequencing, gene transcription was analyzed in peripheral blood mononuclear cells from asymptomatic (n=19) and symptomatic (n=8) <em>T. cruzi</em>-infected individuals, and from non-infected controls (n=15). Differential expression was compared across groups and before/after treatment in <em>T. cruzi</em>-infected subgroups. Transcriptomic changes associated with untreated infection were observed in comparisons with controls, with 12 upregulated and 206 downregulated genes in all the subjects infected with <em>T. cruzi</em>, and 47 upregulated and 215 downregulated genes in the symptomatic group. Very few differentially expressed genes were found after treatment and between the different infected groups. A gene set enrichment analysis highlighted several immune-related pathways activated during the infection, with antiparasitic therapy normalizing immune function after treatment. This matched changes in the kynurenine/tryptophan ratio, increased in pre-treatment samples and suggesting chronic immune fatigue, which was restored following treatment. The described differentially expressed genes can provide insights for the study of new potential biomarkers and pathways associated with disease progression and treatment response.