Dynamics and functional heterogeneity of FOXP3+ regulatory T cells in Trypanosoma cruzi infection: a systematic review.

In 30 seconds

This systematic review synthesised 27 studies of FOXP3+ regulatory T-cell (Treg) phenotype and function in human and experimental Trypanosoma cruzi infection: 9 human studies and 18 murine studies. Human evidence linked indeterminate Chagas disease with functionally stable Tregs enriched for CD39, high CD25 and CTLA-4, whereas cardiomyopathy was associated with Treg instability, increased PD-1 and partial Th1-like features. In mice, transient Treg restriction during acute infection enhanced CD8+ T-cell-mediated parasite control, while failure to restore regulatory balance promoted chronic cardiac inflammation. The findings support a phase-dependent, dual role for Tregs.

Key findings

• The review included 27 studies: 9 in humans and 18 in murine models.
• Indeterminate Chagas disease was associated with stable Tregs enriched for CD39, high CD25 and CTLA-4.
• Chagas cardiomyopathy was associated with Treg instability, PD-1 upregulation and partial acquisition of Th1-like features.
• In mice, transient acute-phase Treg restriction enhanced CD8+ T-cell-mediated parasite control, while persistent regulatory imbalance promoted chronic cardiac inflammation.

Why it matters

The review highlights that Treg activity may have different implications across disease stages: limiting immune-mediated cardiac injury may come at the cost of parasite control, while inadequate regulation may contribute to chronic inflammation. This framework helps interpret immune findings in Chagas disease and identifies Treg-associated signatures, including CD39 expression and activated/resting Treg ratios, as candidates for further study.

What to keep in mind

The evidence combines human and murine studies, and the abstract does not report pooled quantitative estimates; findings may therefore reflect heterogeneous evidence rather than a single clinical effect.