MAMMALIAN TARGET OF RAPAMYCIN (MTOR) PATHWAY, A POTENTIAL REGULATOR OF MACROPHAGE POLARIZATION IN TRYPANOSOMA CRUZI INFECTION

RUTH BAIGORRI ; JORGE ROJAS M ; CINTHIA STEMPIN ; FABIO CERBÁN

Congreso; REUNIÓN DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA; 2013

Macrophages (Mo) play a key role in the control of intracellular T. cruzi replication. Previously we have shown that T. cruzi modulates Mo polarization through the induction of arginase and upregulation of coinhibitors molecules such as PD-Ls. It is known that mTOR pathway is activated by a decreased in the concentration of amino acids or increased production of urea. Therefore, the aim of this work was to study the role of mTOR in Mo polarization and T. cruzi replication. To do that, Mo from different sources such as J774 cells, Bone Marrow Derived Mo and Peritoneal Mo were pretreated with mTOR pharmacological inhibitors: Rapamicin (Rap), LY294002 and PP242 and then infected with T. cruzi trypomastigotes. While Rap prevents mTOR complex formation, PP242 inhibits its kinase activity and LY294002 is a PI3K inhibitor which is upstream of mTOR. First, we examined the effect of mTOR inhibition in parasite replication. We found that all pretreatment decreased parasite replication (p