. INHIBITION OF WNT SIGNALING PATHWAY CONTROLS PARASITE REPLICATION AND INFECTION-INDUCED PATHOLOGY DURING TRYPANOSOMA CRUZI INFECTION

VOLPINI, XIMENA; AMBROSIO, LF; FOZZATTI, LAURA; INSFRAN, CONSTANZA; MOTRAN, CLAUDIA C

Mar del Plata

Congreso; LXI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC) LXIV REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI); 2016

SAIC-SAI

During the very early stages of T. cruzi infection, this parasite isfound within macrophages (Mo), where its replication can be eitherinhibited or favored, leading to dissemination to other sites withinthe body. Experimental evidence indicates that control of T. cruziparasitism during the early phase of infection is critically dependenton effective Mo activation. Wnt signaling, essential for embryonicdevelopment, has also recently been involved in the regulationof inflammatory processes. This signaling pathway is induced inMo by inflammatory stimulus and depending on the compositionof Wnt//Frizzled (Fz) complex, non-canonical or Wnt/b-catenin(canonical) pathways are initiated leading to amplify or controlthe inflammation, respectively. In addition, the role of canonicalpathway on effector and regulatory T cells is controversial. Wehave reported that canonical Wnt signaling is activated in spleenand Mo after T. cruzi infection in vivo and in vitro respectively,with this pathway inhibition in Mo controlling intracellular parasitereplication. In this study we tested the hypothesis that thepharmacological modulation of Wnt signaling pathway during T.cruzi infection might limit parasite replication and also infectioninduced-pathology. In vitro canonical Wnt pathway inhibition bytreatment of infected Mo with iCRT14 or CCT036477 increasedthe secretion of pro-inflammatory cytokines and was more effectiveto inhibit parasite replication (p