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Trypomastigotes and amastigotes of Trypanosoma cruzi induce apoptosis and STAT3 activation in cardiomyocytes in vitro

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Abstract

The haemoflagellate Trypanosoma cruzi is the causative agent of Chagas’ disease that occurs in approximately 8 million people in Latin America. Patients infected with T. cruzi frequently suffer of cardiomegaly and may die of myocardial failure. Here we show that T. cruzi trypomastigotes (extracellular form) increased in vitro apoptosis of rat cardiomyocytes. Additionally, we demonstrated that amastigotes (intracellular form), for which a method for purification was established, were also able to induce cardiomyocyte apoptosis. Increase of apoptosis was associated with up-regulation of the apoptotic gene bax by trypomastigotes, while expression of the anti-apoptotic gene bcl-2 was down-regulated by amastigotes. The transcription factor STAT3 but not STAT1 was activated in cardiomyocytes by trypomastigotes. In addition, tlr7 gene expression was up-regulated in cardiomyocytes incubated with trypomastigotes, suggesting that this Toll-like receptor is involved in the intracellular recognition after host cell invasion by T. cruzi. Glycosylphosphatidylinositols purified from trypomastigotes did not induce cardiomyocyte apoptosis and STAT activation but down-regulated tlr7 gene expression. In conclusion, cardiomyopathy observed in Chagas’ disease might be in part due to apoptosis of cardiomyocytes induced directly by the parasite.

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Acknowledgments

This work was supported by the Deutsche Stiftung für Herzforschung (to F.D.-G., R.T.S., and B.M.), Alumni Medizin Marburg e.V. (to P.S.), Roland und Elfriede Schauer-Stiftung (to P.S.), Studienstiftung des Deutschen Volkes (to P.S.), BMBF BRA 07/046 (to R.T.S. and M.A.C.), NIH 1RO1AI071319-01 (to R.T.G.), INCTV/CNPq 573547/2008-4/FAPEMIG CBB—APQ-00077-09 (to R.T.G. and M.A.C.), FAPEMIG CBB—APQ-01603-09 (to M.A.C.), and the program PROBRAL of DAAD/CAPES (to R.T.S. and R.T.G.).

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Authors and Affiliations

  1. Laboratory of Parasitology, Institute for Virology, Philipps University, 35043, Marburg, Germany

    Philipp Stahl, Jörg Schmidt, Ralph T. Schwarz & Françoise Debierre-Grockiego

  2. Department of Cardiology, Philipps University, 35033, Marburg, Germany

    Volker Ruppert, Thomas Meyer & Bernhard Maisch

  3. Department of Psychosomatic Medicine and Psychotherapy, Georg August University, 37075, Göttingen, Germany

    Thomas Meyer

  4. Research Centre René Rachou, FIOCRUZ, Belo Horizonte, MG, 30190-002, Brazil

    Marco A. Campos & Ricardo T. Gazzinelli

  5. Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA

    Ricardo T. Gazzinelli

  6. Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, 31270-910, Brazil

    Ricardo T. Gazzinelli

  7. CNRS-UMR 8576, Unit of Structural and Functional Glycobiology, Univ Lille Nord de France, Lille, 59000, France

    Ralph T. Schwarz

  8. Université François Rabelais de Tours, UMR 1282 Infectiologie et Santé Publique, Tours, 37200, France

    Françoise Debierre-Grockiego

  9. INRA, UMR 1282 Infectiologie et Santé Publique, Nouzilly, 37380, France

    Françoise Debierre-Grockiego

Authors
  1. Philipp Stahl
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  2. Volker Ruppert
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  8. Ralph T. Schwarz
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  9. Françoise Debierre-Grockiego
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Corresponding author

Correspondence to Françoise Debierre-Grockiego.

Additional information

Philipp Stahl and Volker Ruppert contributed equally to this work. A part of this work is presented as a partial fulfilment of the requirements of the doctoral thesis (Dr. rer. nat.) of Philipp Stahl.

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Stahl, P., Ruppert, V., Meyer, T. et al. Trypomastigotes and amastigotes of Trypanosoma cruzi induce apoptosis and STAT3 activation in cardiomyocytes in vitro. Apoptosis 18, 653–663 (2013). https://doi.org/10.1007/s10495-013-0822-x

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