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

Authors: Silva, Maria C  Davoli-Ferreira, Marcela  Medina, Tiago S  Sesti-Costa, Renata  Silva, Grace K  Lopes, Carla D  Cardozo, Lucas E  Gava, Fábio N  Lyroni, Konstantina  Dias, Fabrício C  Frade, Amanda F  Baron, Monique  Nakaya, Helder I  Figueiredo, Florêncio  Alves-Filho, José C  Cunha, Fernando Q  Tsatsanis, Christos  Chevillard, Christophe  Cunha-Neto, Edecio  Hirsch, Emilio  Silva, João S  Cunha, Thiago M 
Citation: Silva MC, etal., Nat Commun. 2018 Apr 17;9(1):1513. doi: 10.1038/s41467-018-03986-3.
Pubmed: (View Article at PubMed) PMID:29666415
DOI: Full-text: DOI:10.1038/s41467-018-03986-3

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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RGD Object Information
RGD ID: 38599151
Created: 2020-09-10
Species: All species
Last Modified: 2020-09-10
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.