IN VIVO PHARMACOLOGICAL INHIBITION OF WNT PROTEINS SECRETION DURING THE ACUTE PHASE OF T. CRUZI INFECTION REDUCES THE SEVERITY OF CHRONIC CHAGAS DISEASE CARDIOMYOPATHY IN BALB/C MICE.

VOLPINI, XIMENA; AMBROSIO, LAURA; BRAJIN, AGUSTINA; AOKI, MARIA DEL PILAR; RIVAROLA, HÉCTOR WALTER; ALFONSO, FERNANDO; FOZZATTI, LAURA; MOTRÁN, CRISTINA

Mar del Plata

Congreso; LXVI Reunión Anual de la Sociedad Argentina de Inmunología; 2018

Sociedad Argentina de Inmunología

Chagas disease is a major cause of heart disease and cardiovascular-related deaths in endemic areas located in Latin America. Each year there are approximately 12,000 deaths which are attributable to Chagas disease,typically due to severe chronic Chagas disease cardiomyopathy. Wnt signaling, essential for embryonic development, has also recently been involved in the regulation of inflammatory processes. We have previously reported that T. cruzi infection induces Wnt pathways activation and that in vivo pharmacological inhibition of the Wnt proteins secretion controls the parasite replication and improve the survival of lethally infected B6 mice. To investigate the role on Wnt proteins in determining the outcome of chronic Chagas disease, BALB/c mice were infected with 1,000 trypomastigotes of T. cruzi and treated with the inhibitor of Wnt secretion IWP-L6 (7.5 mg/kg) or vehicle (control) on days 5, 8, 11 and 14 post-infection (pi). During the acute phase of the infection, IWP-L6-treated mice showed lower levels of parasitemia (p<0.05), associated with increased serum levels of IL-12 (p<0.05) and TNF (p<0.001) and decreased function of Treg cells (p<0.05) compared with control mice. At thechronic phase of the infection (180 days pi), the cardiacelectrophysiology and global left ventricular function (LV) were studied by electrocardiogram (ECG) and 2D-echocardiogram (ECHO), respectively. The ECGs of IWP-L6-treated mice were improved compared with control mice, because non-treated group presented a significant prolongation in the QT intervals (p<0.001), suggesting intraventricular conduction blockages; meanwhile, this abnormality was not observed in the IWP-L6-treated group. In addition, ECHO revealed systolic disfunction that was only present in control mice (p<0.01). Our results indicate that the inhibition of Wnt proteins secretion during the acute phase of the infection might controls parasite replication, thus preventing the development of chronic cardiomyopathy.