Canonical PI3Kγ signaling in myeloid cells restricts Trypanosoma cruzi infection and dampens chagasic myocarditis - Archive ouverte HAL Access content directly
Journal Articles Nature Communications Year : 2018

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

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Marcela Davoli-Ferreira
  • Function : Author
Tiago Medina
  • Function : Author
Renata Sesti-Costa
  • Function : Author
Grace Silva
  • Function : Author
Lucas Cardozo
  • Function : Author
Fábio Gava
  • Function : Author
Konstantina Lyroni
  • Function : Author
Amanda Farage Frade
  • Function : Author
  • PersonId : 950024
Monique Baron
  • Function : Author
  • PersonId : 959141
Florêncio Figueiredo
  • Function : Author
José Alves-Filho
  • Function : Author
Fernando Cunha
  • Function : Author
Christos Tsatsanis
  • Function : Author
Edecio Cunha
  • Function : Author
Thiago Cunha
  • Function : Author

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.
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hal-01784218 , version 1 (10-01-2019)

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Attribution - CC BY 4.0

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Maria M Silva, Marcela Davoli-Ferreira, Tiago Medina, Renata Sesti-Costa, Grace Silva, et al.. Canonical PI3Kγ signaling in myeloid cells restricts Trypanosoma cruzi infection and dampens chagasic myocarditis. Nature Communications, 2018, 9 (1), ⟨10.1038/s41467-018-03986-3⟩. ⟨hal-01784218⟩

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