Transcriptomic Evidence of Immune Modulation in Subjects With Chronic Trypanosoma cruzi Infection.

Area of Science:

• Molecular Biology
• Immunology
• Infectious Diseases

Background:

• Chagas disease, caused by Trypanosoma cruzi, is a significant global health concern.
• Understanding the host's transcriptomic response is crucial for identifying disease mechanisms and therapeutic targets.

Purpose of the Study:

• To investigate gene expression changes in Chagas disease patients before and after treatment.
• To identify potential biomarkers and pathways involved in disease progression and treatment response.

Main Methods:

• Total RNA sequencing of peripheral blood mononuclear cells from infected individuals and controls.
• Differential gene expression analysis comparing infected and non-infected groups, and pre- vs. post-treatment.
• Gene set enrichment analysis and assessment of the kynurenine to tryptophan ratio.

Main Results:

• Untreated infection significantly altered gene expression, with more downregulated than upregulated genes, particularly in symptomatic patients.
• Treatment led to normalization of immune-related pathways and restoration of the kynurenine to tryptophan ratio.
• Few differentially expressed genes were observed post-treatment or between infected groups.

Conclusions:

• Transcriptomic analysis reveals significant immune dysregulation in Chagas disease, characterized by chronic immune fatigue.
• Treatment effectively modulates the host's immune response, offering insights into disease management.
• Identified gene expression patterns may serve as potential biomarkers for Chagas disease progression and treatment efficacy.