TRYPANOSOMA CRUZI INFECTION: ROLE OF WNT SIGNALING IN CARDIAC MACROPHAGES POLARIZATION

BRUGO, MARÍA BELÉN; QUIROZ, JUAN NAHUEL; VOLPINI, XIMENA; BAIGORRI RUTH; ABRATE CAROLINA PAOLA; MOTRÁN, CRISTINA

Congreso; Reunión de Biociencias 201; 2021

Chagas cardiomyopathy represents the most frequent and seriouscomplication of chronic Chagas disease, affecting about 20-30% ofpatients. Cardiac inflammation and tissue damage is orchestrated bythe infiltration and activation of immune cells including macrophages(Mo) into the myocardium. Mo with M1 phenotype (F4/80+ CD11b+CD86+ CD206−) predominate at short times post infection (pi)and then they are rapidly polarized toward M2 phenotype (F4/80+CD11b+ CD86− CD206+) which remains sustained during the infection.We have showed that in vivo inhibition of Wnt signaling bytreatment with IWP-L6 (an inhibitor of Wnt proteins secretion) duringthe acute phase of T. cruzi infection controls the parasite replication,inhibits the development of parasite-prone and fibrosis-prone Th2-type immune response, and prevents the development of chronicChagas disease’s cardiac abnormalities. To investigate the role ofWnt signaling in the modulation of cardiac infiltrating Mo phenotype,BALB/c mice infected with 1,000 trypomastigotes of T. cruzi andtreated with IWP-L6 (7.5 mg/kg) or vehicle (control) on days 5, 8,11 and 14 pi were sacrificed at day 17 pi. Heart Mo isolated by a sequentialcombination of washing, mechanical disruption, enzymaticdigestion, and density centrifugation using Percoll were stained withappropriate antibodies to determine the phenotype by flow cytometry. Results were analyzed with FlowJo (V10.7) using One-wayANOVA and Tukey’s test for multiple comparison. We found that T.cruzi infection induced an increase of heart Mo (F4/80+ CD11b+)infiltration that was reversed by IWP-L6 treatment (P<0.05). Comparedto non-infected mice, heart of control mice showed increasedfrequency of M1 (F4/80+ CD11b+ CD86+ CD206−) and M2 (F4/80+CD11b+ CD86− CD206+) Mo populations, while cardiac tissue ofIWP-L6-treated mice only showed M1 Mo infiltrate. Thus, theseresults suggest that Wnt signaling participate in the polarization ofcardiac Mo towards M2 phenotype.