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Canonical PI3Kγ signaling in myeloid cells restricts Trypanosoma cruzi infection and dampens chagasic myocarditis

Author

Listed:
  • Maria C. Silva

    (University of Sao Paulo
    University of Sao Paulo
    Universidade Católica Dom Bosco)

  • Marcela Davoli-Ferreira

    (University of Sao Paulo
    University of Sao Paulo)

  • Tiago S. Medina

    (University of Sao Paulo)

  • Renata Sesti-Costa

    (University of Sao Paulo)

  • Grace K. Silva

    (University of Sao Paulo)

  • Carla D. Lopes

    (University of Sao Paulo)

  • Lucas E. Cardozo

    (University of São Paulo)

  • Fábio N. Gava

    (University of Sao Paulo)

  • Konstantina Lyroni

    (University of Crete)

  • Fabrício C. Dias

    (University of Sao Paulo)

  • Amanda F. Frade

    (University of São Paulo
    Brazil University)

  • Monique Baron

    (University of São Paulo)

  • Helder I. Nakaya

    (University of São Paulo)

  • Florêncio Figueiredo

    (University of Brasilia, Campus Universitário Darcy Ribeiro)

  • José C. Alves-Filho

    (University of Sao Paulo)

  • Fernando Q. Cunha

    (University of Sao Paulo)

  • Christos Tsatsanis

    (University of Crete)

  • Christophe Chevillard

    (Aix Marseille Université AMU, Parc Scientifique de Luminy case 928)

  • Edecio Cunha-Neto

    (University of São Paulo
    University of São Paulo
    Institute of Investigation in Immunology-iii/INCT)

  • Emilio Hirsch

    (University of Torino)

  • João S. Silva

    (University of Sao Paulo)

  • Thiago M. Cunha

    (University of Sao Paulo)

Abstract

Chagas disease is caused by infection with the protozoan Trypanosoma cruzi (T. cruzi) and is an important cause of severe inflammatory heart disease. However, the mechanisms driving Chagas disease cardiomyopathy have not been completely elucidated. Here, we show that the canonical PI3Kγ pathway is upregulated in both human chagasic hearts and hearts of acutely infected mice. PI3Kγ-deficient mice and mutant mice carrying catalytically inactive PI3Kγ are more susceptible to T. cruzi infection. The canonical PI3Kγ signaling in myeloid cells is essential to restrict T. cruzi heart parasitism and ultimately to avoid myocarditis, heart damage, and death of mice. Furthermore, high PIK3CG expression correlates with low parasitism in human Chagas’ hearts. In conclusion, these results indicate an essential role of the canonical PI3Kγ signaling pathway in the control of T. cruzi infection, providing further insight into the molecular mechanisms involved in the pathophysiology of chagasic heart disease.

Suggested Citation

  • Maria C. Silva & Marcela Davoli-Ferreira & Tiago S. Medina & Renata Sesti-Costa & Grace K. Silva & Carla D. Lopes & Lucas E. Cardozo & Fábio N. Gava & Konstantina Lyroni & Fabrício C. Dias & Amanda F., 2018. "Canonical PI3Kγ signaling in myeloid cells restricts Trypanosoma cruzi infection and dampens chagasic myocarditis," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03986-3
    DOI: 10.1038/s41467-018-03986-3
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