mTOR inhibition in Trypanosoma cruzi infected macrophages actives NLRP3 and induces mitochondrial ROS production that regulate parasite survival

ROJAS MÁRQUEZ, JD; ANA, Y; STEMPIN, CC; CERBAN FM

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

We have previously shown that Trypanosoma cruzi infection in macrophages (Mo) activates mTOR pathway and its inhibition decreased parasite replication. However, in rapamycin (Rap) pretreated and T. cruzi infected Mo, we observed reduced nitric oxide production and iNOS expression compared to control cells. Therefore, the aim of this work was to determine alternative activated mechanisms involved in controlling parasite during mTOR inhibition. In this sense, we found that cytoplasmic ROS (cROS) as well as IDO activity were not involved as inflammatory mechanisms. Consequently, to study possible mediators involved in parasite killing, we obtained bone marrow derived Mo (BMDM) from different KO mice pretreated them with Rap and then infected. Parasite load was evaluated 72h post infection (pi) by immunofluorescencia (IF). The results showed a significant increase in parasite load in BMDM from IL-6-KO, TNFa-R-KO and NLRP3-KO compared to WT BMDM. However, parasite number stands out in BMDM from NLRP3 KO (p