Skip to Main content Skip to Navigation
Journal articles

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

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.
Complete list of metadatas

Cited literature [52 references]  Display  Hide  Download

https://hal-amu.archives-ouvertes.fr/hal-01784218
Contributor : Christophe Chevillard <>
Submitted on : Thursday, January 10, 2019 - 4:34:26 PM
Last modification on : Monday, June 10, 2019 - 6:02:40 PM
Long-term archiving on: : Thursday, April 11, 2019 - 5:21:07 PM

File

s41467-018-03986-3.pdf
Publication funded by an institution

Licence


Distributed under a Creative Commons Attribution 4.0 International License

Identifiers

Collections

Citation

Maria 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, Nature Publishing Group, 2018, 9 (1), ⟨10.1038/s41467-018-03986-3⟩. ⟨hal-01784218⟩

Share

Metrics

Record views

119

Files downloads

91