ROLE OF WNT SIGNALING IN THE METABOLIC REPROGRAMMING OF Trypanosoma cruzi INFECTED MACROPHAGES

AMBROSIO, LAURA F.; VOLPINI, XIMENA; CLAUDIA MOTRAN; BRUGO, MB; NICOLAS PONCE

Tucuman

Congreso; LXVII Reunion Anual SAI; 2019

SAI

Changes in metabolic profiles are associated in macrophages (Mo) with activation and function,with M1 and M2 Mo preferentially using glycolysis or oxidative phosphorylation (OXPHOS) asenergy source, respectively. We have reported that T. cruzi infection induces β-catenin andWnt/Ca+2 pathways activation in Mo, with these pathways being critical to sustainingintracellular parasite replication. Moreover, inhibition of β-catenin or Wnt proteins secretionbefore infection modulates Mo activation status towards a more microbicidal phenotype thanclassical M1 (M1-like). Also, RNA-seq preliminary analysis demonstrated that both subtypes ofM1-like could be new subtypes, different from the classic M1. This study aims to evaluate somekey events of glucose metabolism in M1-like in comparison with the classical M1. For that, theexpression of glucose transporter gene (Slc2a1) and protein (GLUT-1), glucose uptake and ATPproduction were evaluated in bone marrow-derived Mo from B6 mice that were treated withLPS-IFN-γ (M1), inhibitors of β-catenin (iCRT, CCT) or Wnt proteins secretion (IWP-L6), orvehicle (I) 24 h before T. cruzi infection, and vehicle-treated uninfected Mo (NI). Although theexpression of GLUT-1 and Slc2a1 showed no significant changes, T. cruzi infection inducedsignificant glucose uptake (2NBDG uptake) (p