HIF‐1α and CD73 expression in cardiac leukocytes correlates with the severity of myocarditis in end‐stage Chagas disease patients

EBERHARDT, NATALIA; SANMARCO, LILIANA MARIA; BERGERO, GASTÓN; FAVALORO, ROBERTO RENÉ; VIGLIANO, CARLOS; AOKI, MARIA PILAR

JOURNAL OF LEUKOCYTE BIOLOGY

FEDERATION AMER SOC EXP BIOL

Año: 2021

0741-5400

Chronic Chagas cardiomyopathy is the main infectious myocarditis worldwide. Almost 30% ofTrypanosoma cruzi infected individuals develop slow and progressive myocarditis that leads toventricular dilation and heart failure. Heart transplantation is an established, valuable therapeutic option for end-stage Chagas disease patients. Although the pathophysiology of Chagasdisease has been addressed for decades by numerous groups, the cardiac immunologic mechanisms involved in the progression of clinical manifestation are still unknown. Growing evidencedemonstrates that hypoxia-inducible factor (HIF)-1𝛼 plays indispensable roles in driving immuneresponse by triggering the expression of CD73 purinergic ecto-enzyme. Purinergic system controls the duration and magnitude of purine signals directed to modulate immune cells through theconversion of extracellular ATP (microbicide/proinflammatory) to the immunoregulatory metabolite adenosine. In the present work, we described that infiltrating leukocytes within cardiacexplants from patients with end-stage Chagas cardiomyopathy up-regulated HIF-1𝛼 and CD73expression. Moreover, the number of HIF-1𝛼+ and CD73+ leukocytes positively correlated withthe myocarditis severity and the local parasite load. Furthermore, we demonstrated a direct relationship between tissue parasite persistence and the influx of immune cells to the infected hearts,which ultimately determine the severity of the myocarditis. These findings provide evidence thatCD73-dependent regulatory pathways are locally triggered in the myocardium of patients withend-stage Chagas disease