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Tolerogenic Dendritic Cells Reduce Cardiac Inflammation and Fibrosis in Chronic Chagas Disease

Emanuelle de Souza Santos1, Luciana Souza de Aragão-França2, Cássio Santana Meira1

  • 1Gonçalo Moniz Institute, FIOCRUZ, Salvador, Brazil.

Frontiers in Immunology
|April 23, 2020
PubMed

Insights

Tolerogenic dendritic cells (tDCs) show therapeutic potential for chronic Chagas disease cardiomyopathy (CCC). Treatment with tDCs reduced heart inflammation, fibrosis, and disease progression in a mouse model, offering a promising new avenue for CCC treatment.

Area of Science:

  • Immunology
  • Cardiology
  • Parasitology

Background:

  • Chronic Chagas disease cardiomyopathy (CCC) is a severe complication of Chagas disease, leading to heart failure.
  • Dendritic cells (DCs) play a crucial role in regulating immune responses, suggesting potential therapeutic applications.

Purpose of the Study:

  • To investigate the therapeutic potential of tolerogenic dendritic cells (tDCs) in an experimental model of Chagas disease cardiomyopathy.
  • To assess the impact of tDCs on immune cell populations and inflammatory markers associated with CCC progression.

Main Methods:

  • Tolerogenic dendritic cells (tDCs) were generated and characterized by specific surface markers (CD11b+, CD11c+, low MHC-II, CD86, CD80, CD40, high PD-L) and cytokine production (low IL-6, IL-12p70; high IL-10).
  • tDCs' effects on lymphoproliferation and regulatory T cell (Treg) induction were assessed *in vitro*.
  • A mouse model of CCC was used to evaluate the therapeutic efficacy of tDCs, measuring heart inflammation, fibrosis, gene expression of cytokines and cardiac remodeling markers, and Treg cell infiltration.

Main Results:

  • tDCs exhibited tolerogenic properties, inhibiting lymphoproliferation and increasing FoxP3+ Treg cells *in vitro*.
  • Treatment with tDCs significantly reduced heart inflammation and fibrosis in the mouse model of CCC.
  • tDCs administration decreased pro-inflammatory cytokine gene expression (Ifng, Il12) and cardiac remodeling genes (Col1a2, Lgals3), while upregulating IL-10 gene expression.
  • Increased percentages of Treg cells were observed in the hearts and spleens of chagasic mice treated with tDCs.

Conclusions:

  • Tolerogenic dendritic cells demonstrate significant therapeutic potential for mitigating chronic Chagas disease cardiomyopathy.
  • tDCs effectively inhibit key pathological processes in CCC, including inflammation, fibrosis, and pro-inflammatory cytokine production.
  • The immunomodulatory effects of tDCs, particularly their ability to promote Treg cells, underlie their efficacy in treating experimental CCC.

Keywords:
Chagas diseaseTrypanosoma cruziantigen presenting cellscardiomyopathyfibrosisinflammation

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