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


  • Silva Maria M
  • Davoli-Ferreira Marcela
  • Medina Tiago
  • Sesti-Costa Renata
  • Silva Grace
  • Lopes Carla
  • Cardozo Lucas
  • Gava Fábio
  • Lyroni Konstantina
  • Dias Fabrício
  • Frade Amanda Farage
  • Baron Monique
  • Nakaya Helder
  • Figueiredo Florêncio
  • Alves-Filho José
  • Cunha Fernando
  • Tsatsanis Christos
  • Chevillard Christophe
  • Cunha Edecio
  • Hirsch Emilio
  • Silva João Nuno
  • Cunha Thiago


  • Chagas disease
  • Protozoan infections
  • Heart disease
  • Cardiomyopathy
  • Canonical
  • Mice
  • Molecular mechanisms

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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.

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