Wnt Signalling Orchestrates the Immune Response and Cardiac Damage During Trypanosoma cruzi Infection

VOLPINI X; AMBROSIO LF; BRAJIN MA; BRUGO MB; AOKI MP; RIVAROLA HW; ALONSO F; FOZZATTI L; CERVI, LAURA; MOTRAN C.C.

ACS Infection Diseases

American Chemical Society

Año: 2021

Chagas cardiomyopathy is the consequence of acompromised electrical and mechanical cardiac function, withparasite persistence, unbalanced inflammation, and pathologicaltissue remodelling, being intricately related to myocardial aggressionand impaired function. Recent studies have shown that Wnt signalingpathways play a critical role in the pathogenesis of cardiac andvascular diseases. In addition, we have reported that Trypanosomacruzi infection activates Wnt signaling to promote intracellularreplication of the parasites in macrophages, with the treatment ofmice with IWP-L6 (an inhibitor of the O-acyl-transferase, PORCN,responsible for the post-translational modifications necessary for Wntprotein secretion) being able to diminish parasitemia and tissueparasitism. Here, we show that inhibition of Wnt signaling during theacute 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 cardiac abnormalities characteristics of chronic Chagas disease. Our resultssuggest that the Wnt signaling pathway might be a potential target to prevent the development of T. cruzi-induced cardiomyopathy.