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HIF‐1α and CD73 expression in cardiac leukocytes correlates with the severity of myocarditis in end‐stage Chagas disease patients
Author(s) -
Eberhardt Natalia,
Sanmarco Liliana Maria,
Bergero Gastón,
Favaloro Roberto René,
Vigliano Carlos,
Aoki Maria Pilar
Publication year - 2021
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.4ma0420-125r
Subject(s) - myocarditis , chagas disease , biology , immunology , viral myocarditis , immune system , cardiomyopathy , purinergic receptor , trypanosoma cruzi , heart failure , adenosine , medicine , virus , endocrinology , parasite hosting , world wide web , computer science
Chronic Chagas cardiomyopathy is the main infectious myocarditis worldwide. Almost 30% of Trypanosoma cruzi infected individuals develop slow and progressive myocarditis that leads to ventricular dilation and heart failure. Heart transplantation is an established, valuable therapeutic option for end‐stage Chagas disease patients. Although the pathophysiology of Chagas disease has been addressed for decades by numerous groups, the cardiac immunologic mechanisms involved in the progression of clinical manifestation are still unknown. Growing evidence demonstrates that hypoxia‐inducible factor (HIF)‐1α plays indispensable roles in driving immune response 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 the conversion of extracellular ATP (microbicide/proinflammatory) to the immunoregulatory metabolite adenosine. In the present work, we described that infiltrating leukocytes within cardiac explants from patients with end‐stage Chagas cardiomyopathy up‐regulated HIF‐1α and CD73 expression. Moreover, the number of HIF‐1α+ and CD73+ leukocytes positively correlated with the 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 that CD73‐dependent regulatory pathways are locally triggered in the myocardium of patients with end‐stage Chagas disease.