T. CRUZI INFECTION INDUCES FIRST WNT/Β-CATENIN AND THEN WNT/CA+2 PATHWAYS ACTIVATION IN MACROPHAGES WHICH FAVOUR THE PARASITE REPLICATION

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

CABA

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

SAIC-SAI

Many studies have demonstrated that T. cruzi utilize thehost Ca+2 signalling to establish the infection and several mechanismshave been proposed to explain the intracellular Ca+2 influxthat occurs during this infection. In addition, it has been reportedthat NFATc1 is activated in response to T. cruzi infection in a TLR-independentmanner but the critical molecules and signalling pathwaysthat lead to NFATc1 activation have not yet been identified.Wnt signalling, essential for embryonic development, has recentlybeen involved in the regulation of inflammatory processes. This signalling signallingpathway is induced in macrophages (Mo) by inflammatorystimulus and depending on the composition of Wnt/Fdz complex,Wnt/β catenin or Wnt/Ca+2 pathways are initiated leading to amplifyor control the inflammation. We have reported that after the recognitionof T. cruzi by TLR in Mo, the expression of Wnt proteins and Fdzreceptors are induced and Wnt/β-catenin pathway is activated, withthe specific inhibition of this pathway or the inhibition of Wnt proteinssecretion controlling the T. cruzi intracellular replication. In thisstudy, we tested the hypothesis that Wnt proteins secreted after theinfection might also activate Wnt/Ca+2 pathway with this pathway beingresponsible for the infection-induced NFATc1 activation. Westernblot and immunofluorescence assays revealed that in vitro infectedMo up-regulates the expression of p-CAMKII (Thr286) and activeNFATc1 (p