Role of dystrophin in acute Trypanosoma cruzi infection

Lygia M. Malvestio, Mara R.N. Celes, Cristiane Milanezi, João S. Silva, Linda A. Jelicks, Herbert B. Tanowitz, Marcos A. Rossi, Cibele M. Prado

Research output: Contribution to journalArticle

3 Scopus citations

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 invivo and invitro 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 20dpi confirmed by invitro 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.

Original languageEnglish (US)
Pages (from-to)768-777
Number of pages10
JournalMicrobes and Infection
Volume16
Issue number9
DOIs
StatePublished - Sep 1 2014

Keywords

  • Calpain-1
  • Cardiomyocytes
  • Chagas disease
  • Dystrophin
  • Inflammation
  • Trypanosoma cruzi

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Infectious Diseases

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  • Cite this

    Malvestio, L. M., Celes, M. R. N., Milanezi, C., Silva, J. S., Jelicks, L. A., Tanowitz, H. B., Rossi, M. A., & Prado, C. M. (2014). Role of dystrophin in acute Trypanosoma cruzi infection. Microbes and Infection, 16(9), 768-777. https://doi.org/10.1016/j.micinf.2014.07.010