Mammalian target of rapamycin inhibition in Trypanosoma cruzi-infected macrophages leads to an intracellular profile that is detrimental for infection

MÁRQUEZ, JORGE DAVID ROJAS; ANA, YAMILE; BAIGORRÍ, RUTH ELIANA; STEMPI, CINTHIA CAROLINA; CERBAN, FABIO MARCELO

Frontiers in Immunology

Frontiers Media S.A.

Año: 2018 vol. 9

he causative agent of Chagas´ disease, Trypanosoma cruzi, affects approximately 10 million people living mainly in Latin America, with macrophages being one of the first cellular actors confronting the invasion during T. cruzi infection and their function depending on their proper activation and polarization into distinct M1 and M2 subtypes. Macrophage polarization is thought to be regulated not only by cytokines and growth factors but also by environmental signals. The metabolic checkpoint kinase mammalian target of rapamycin (mTOR)-mediated sensing of environmental and metabolic cues influences macrophage polarization in a complex and as of yet incompletely understood manner. Here, we studied the role of the mTOR pathway in macrophages during T. cruzi infection. We demonstrated that the parasite activated mTOR, which was beneficial for its replication since inhibition of mTOR in macrophages by different inhibitors decreased parasite replication. Moreover, in rapamycin pretreated and