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

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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

Edité par CCSD ; Nature Publishing Group -

International audience. 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 toT. 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 lowparasitism 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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