Signatures of CD4⁺ T and B cells are associated with distinct stages of chronic chagasic cardiomyopathy

Area of Science:

• Immunology
• Parasitology
• Infectious Diseases

Background:

• Chagas disease, caused by *Trypanosoma cruzi*, is a neglected parasitic infection affecting millions worldwide.
• While many remain asymptomatic, approximately 30% of infected individuals develop Chronic Chagasic Cardiomyopathy (CCC).
• Understanding the immune cell dynamics in chronic Chagas disease is crucial for identifying disease progression markers.

Purpose of the Study:

• To investigate the alterations in CD4+ T and B cell compartments during the chronic phase of Chagas disease.
• To compare immune cell profiles across asymptomatic, mild CCC, and moderate/severe CCC clinical forms.
• To elucidate the role of specific immune cell subsets in Chagas disease pathogenesis.

Main Methods:

• High-dimensional flow cytometry was utilized to analyze CD4+ T and B cell populations.
• Patient samples included individuals in the chronic phase of Chagas disease with varying cardiac involvement (asymptomatic, mild, moderate/severe).
• Comparative analysis was performed against healthy donors (CTL).

Main Results:

• Effector CD4+ T cells were expanded in both mild and moderate/severe CCC groups.
• Mild CCC patients exhibited increased frequencies of effector memory and T follicular helper (Tfh) cells compared to controls.
• Expansion of activated, differentiated, and exhausted CD4+ T cells and class-switched/atypical memory B cells was noted, particularly in mild CCC.
• All CCC forms showed reduced frequencies of resting CD4+ T cells compared to controls.

Conclusions:

• *Trypanosoma cruzi* infection induces significant changes in CD4+ T and B cell compartments.
• Immune alterations are more pronounced in the mild CCC clinical form, suggesting orchestrated cellular communication.
• Findings underscore the heterogeneity of immune responses in chronic Chagas disease and may offer novel diagnostic or therapeutic targets.