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Updated: Mar 25, 2026
Chemical Cartography Approaches to Study Trypanosomatid Infection
Published on: January 21, 2022
Changes in Proteome Profile of Peripheral Blood Mononuclear Cells in Chronic Chagas Disease
Nisha Jain Garg1,2,3, Kizhake V Soman4, Maria P Zago5
1Department of Microbiology and Immunology, University of Texas Medical Branch (UTMB), Galveston, Texas, United States of America.
Insights
This study identifies key protein differences in individuals infected with Trypanosoma cruzi (Tc), distinguishing between asymptomatic carriers and those with chagasic cardiomyopathy. These findings could help predict disease progression in Tc-infected patients.
Area of Science:
- Proteomics
- Immunology
- Cardiovascular Disease
Background:
- Trypanosoma cruzi (Tc) infection causes chagasic cardiomyopathy, but the mechanisms driving disease development in susceptible individuals remain unclear.
- Understanding these pathomechanisms is crucial for identifying individuals at risk of developing severe cardiac complications.
Purpose of the Study:
- To investigate the proteomic differences in peripheral blood mononuclear cells (PBMCs) of individuals with varying Trypanosoma cruzi (Tc) infection statuses.
- To identify molecular signatures associated with asymptomatic infection versus symptomatic chagasic cardiomyopathy.
- To discover potential biomarkers for predicting disease progression.
Main Methods:
- Proteomic analysis of PBMCs from healthy controls, asymptomatic Tc-infected individuals, and symptomatic Tc-infected individuals using two-dimensional gel electrophoresis (2D-GE) and mass spectrometry.
- Ingenuity Pathway Analysis (IPA) to interpret proteomic data and predict molecular pathways.
- MARS-modeling for biomarker identification and classification of disease risk.
Main Results:
- Significant differential abundance of 213 and 199 protein spots in asymptomatic and symptomatic Tc-infected individuals, respectively, compared to controls.
- Identified increased cytoskeletal disorganization and altered immune cell dynamics in all Tc-infected subjects.
- Predicted decreased cell survival and free radical scavenging capacity in symptomatic individuals, with MYC/SP1 transcription factors highlighted as key regulatory targets.
Conclusions:
- The study identified distinct proteomic profiles associated with different stages of Trypanosoma cruzi (Tc) infection.
- A panel of proteins was identified with high predictive success for classifying individuals with and without cardiac involvement.
- These findings offer potential molecular targets and biomarkers for early detection and risk stratification of chagasic cardiomyopathy.
Abstract:
Trypanosoma cruzi (Tc) infection causes chagasic cardiomyopathy; however, why 30-40% of the patients develop clinical disease is not known. To discover the pathomechanisms in disease progression, we obtained the proteome signature of peripheral blood mononuclear cells (PBMCs) of normal healthy controls (N/H, n = 30) and subjects that were seropositive for Tc-specific antibodies, but were clinically asymptomatic (C/A, n = 25) or clinically symptomatic (C/S, n = 28) with cardiac involvement and left ventricular dysfunction. Protein samples were labeled with BODIPY FL-maleimide (dynamic range: > 4 orders of magnitude, detection limit: 5 f-mol) and resolved by two-dimensional gel electrophoresis (2D-GE). After normalizing the gel images, protein spots that exhibited differential abundance in any of the two groups were analyzed by mass spectrometry, and searched against UniProt human database for protein identification. We found 213 and 199 protein spots (fold change: |≥ 1.5|, p< 0.05) were differentially abundant in C/A and C/S individuals, respectively, with respect to N/H controls. Ingenuity Pathway Analysis (IPA) of PBMCs proteome dataset identified an increase in disorganization of cytoskeletal assembly and recruitment/activation and migration of immune cells in all chagasic subjects, though the invasion capacity of cells was decreased in C/S individuals. IPA predicted with high probability a decline in cell survival and free radical scavenging capacity in C/S (but not C/A) subjects. The MYC/SP1 transcription factors that regulate hypoxia and oxidative/inflammatory stress were predicted to be key targets in the context of control of Chagas disease severity. Further, MARS-modeling identified a panel of proteins that had >93% prediction success in classifying infected individuals with no disease and those with cardiac involvement and LV dysfunction. In conclusion, we have identified molecular pathways and a panel of proteins that could aid in detecting seropositive individuals at risk of developing cardiomyopathy.
