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Updated: Apr 26, 2026

In Vitro Drug Screening Against All Life Cycle Stages of Trypanosoma cruzi Using Parasites Expressing β-galactosidase
Published on: November 5, 2021
Role of dystrophin in acute Trypanosoma cruzi infection
Lygia M Malvestio1, Mara R N Celes2, Cristiane Milanezi3
1Department of Pathology, School of Medicine of Ribeirão Preto, University of São Paulo, SP, Brazil.
Abstract:
Previous studies have demonstrated loss/reduction of dystrophin in cardiomyocytes in both acute and chronic stages of experimental Trypanosoma cruzi (T. cruzi) infection in mice. The mechanisms responsible for dystrophin disruption in the hearts of mice acutely infected with T. cruzi are not completely understood. The present in vivo and in vitro studies were undertaken to evaluate the role of inflammation in dystrophin disruption and its correlation with the high mortality rate during acute infection. C57BL/6 mice were infected with T. cruzi and killed 14, 20 and 26 days post infection (dpi). The intensity of inflammation, cardiac expression of dystrophin, calpain-1, NF-κB, TNF-α, and sarcolemmal permeability were evaluated. Cultured neonatal murine cardiomyocytes were incubated with serum, collected at the peak of cytokine production and free of parasites, from T. cruzi-infected mice and dystrophin, calpain-1, and NF-κB expression analyzed. Dystrophin disruption occurs at the peak of mortality and inflammation and is associated with increased expression of calpain-1, TNF-α, NF-κB, and increased sarcolemmal permeability in the heart of T. cruzi-infected mice at 20 dpi confirmed by in vitro studies. The peak of mortality occurred only when significant loss of dystrophin in the hearts of infected animals occurred, highlighting the correlation between inflammation, dystrophin loss and mortality.
Insights
Inflammation during Trypanosoma cruzi infection causes dystrophin loss in heart cells, leading to high mortality rates. This study links inflammation, dystrophin disruption, and cardiac dysfunction in acute Chagas disease.
Area of Science:
- Cardiovascular Research
- Infectious Diseases
- Molecular Biology
Background:
- Dystrophin reduction in cardiomyocytes is observed in Trypanosoma cruzi (T. cruzi) infection.
- Mechanisms of dystrophin disruption during acute T. cruzi infection remain unclear.
Purpose of the Study:
- To investigate the role of inflammation in dystrophin disruption.
- To correlate inflammation and dystrophin loss with mortality during acute T. cruzi infection.
Main Methods:
- In vivo studies: T. cruzi-infected C57BL/6 mice assessed for inflammation, cardiac dystrophin, calpain-1, NF-κB, TNF-α, and sarcolemmal permeability at 14, 20, and 26 days post-infection.
- In vitro studies: Neonatal murine cardiomyocytes incubated with serum from infected mice to analyze dystrophin, calpain-1, and NF-κB expression.
Main Results:
- Dystrophin disruption peaked at 20 days post-infection, coinciding with peak mortality and inflammation.
- Increased expression of calpain-1, TNF-α, and NF-κB, along with heightened sarcolemmal permeability, was observed.
- In vitro studies confirmed the association between serum from infected mice and dystrophin disruption.
Conclusions:
- Inflammation drives dystrophin disruption in the heart during acute T. cruzi infection.
- Dystrophin loss correlates significantly with increased mortality.
- Findings highlight inflammation and dystrophin loss as key factors in acute Chagas disease cardiac pathology.
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08:17Quantitative 3D Imaging of Trypanosoma cruzi-Infected Cells, Dormant Amastigotes, and T Cells in Intact Clarified Organs
Published on: June 23, 2022
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