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

AMBROSIO L; VOLPINI X; MOTRAN CC; BRUGO MB; PONCE NE

San Miguel de Tucumán,

Congreso; LVII REUNIÓN ANUAL SAI 2019; 2019

SOCIEDAD ARGENTINA DE INMUNOLOGÍA

Changes in metabolic profiles are associated in macrophages (Mo) with activation andfunction, with M1 and M2 Mo preferentially using glycolysis or oxidativephosphorylation (OXPHOS) as energy source, respectively. We have reported that T.cruzi infection induces β-catenin and Wnt/Ca+2 pathways activation in Mo, with thesepathways being critical to sustaining intracellular parasite replication. Moreover,inhibition of β-catenin or Wnt proteins secretion before infection modulates Moactivation status towards a more microbicidal phenotype than classical M1 (M1-like).Also, RNA-seq preliminary analysis demonstrated that both subtypes of M1-like couldbe new subtypes, different from the classic M1. This study aims to evaluate some keyevents of glucose metabolism in M1-like in comparison with the classical M1. For that,the expression of glucose transporter gene (Slc2a1) and protein (GLUT-1), glucoseuptake and ATP production were evaluated in bone marrow-derived Mo from B6 micethat were treated with LPS-IFN- (M1), inhibitors of β-catenin (iCRT, CCT) or Wntproteins secretion (IWP-L6), or vehicle (I) 24 h before T. cruzi infection, and vehicle-treated uninfected Mo (NI). Although the expression of GLUT-1 and Slc2a1 showed nosignificant changes, T. cruzi infection induced significant glucose uptake (2NBDGuptake) (p<0.05), with M1 and IWP-L6 showing significant higher uptake than I(p<0.05). As expected, increased ATP production, associated with OXPHOS, wasobserved in I vs NI (p= 0.001), while M1, iCRT, CCT and IWP-L6 showed lower ATPproduction than I (p<0.05), suggesting a role of Wnt signaling in the switch toOXPHOS by T. cruzi infected Mo.