Deficiency of CD73 activity promotes protective cardiac immunity against Trypanosoma cruzi infection but permissive environment in visceral adipose tissue

Eberhardt, Natalia; Sanmarco, Liliana M.; Bergero, Gastón; Theumer, Martín G.; García, Mónica Cristina; Ponce, Nicolás; Cano, Roxana Carolina; Aoki, María Pilar

doi:10.1016/j.bbadis.2019.165592

Cited by 9 publications

(16 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…reported that no expression of the ATP catabolic machinery was detected in cardiomyocytes, but coronary endothelial cells were highly positive for CD39 and a smaller proportion express CD73 in basal conditions. Moreover, our group has reported that in T. cruzi infected murine heart tissue, CD73 expression is primarily observed in immune cells compared to parenchymal cells 33 . Thus, purinergic enzymes could participate in the optimal adaptation of inflammatory immune cells to the infected tissue.…”

Section: Discussionmentioning

confidence: 94%

“…Moreover, our group has reported that in T. cruzi infected murine heart tissue, CD73 expression is primarily observed in immune cells compared to parenchymal cells. 33 Thus, purinergic enzymes could participate in the optimal adaptation of inflammatory immune cells to the infected tissue. Although the adaptive response of T-cells is recognized as a mainstay for the control of T. cruzi infection, 60 several controversies arise on the role of the inflammatory T-cell response in heart damage.…”

Section: Discussionmentioning

confidence: 99%

“…66 and diminish local parasite burden. 33 Considering the limited regenerative capacity of cardiomyocytes, CD73-derived adenosine could be a critical metabolite to protect the heart from excessive inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…In the last decade, significant advances have been made in understanding the immunologic events that take place in T. cruzi -infected myocardium employing murine models. 32,33,83,84…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, CD73 activity regulates antiparasite immune response in a tissue‐dependent manner. In this sense, cardiac tissue is particularly sensitive to CD73‐generated adenosine 33 . Purinergic modulation of immune system is widely described in tumor contexts and in autoimmune diseases, 34,35 but there are few reports in the setting of cardiac infections.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

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

Eberhardt

Sanmarco

Bergero

et al. 2020

Journal of Leukocyte Biology

Self Cite

View full text Add to dashboard Cite

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)-1 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-1 and CD73 expression. Moreover, the number of HIF-1 + 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.

show abstract

Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…In the last decade, significant advances have been made in understanding the immunologic events that take place in T. cruzi -infected myocardium employing murine models. 32,33,83,84…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Eberhardt

Sanmarco

Bergero

et al. 2020

Journal of Leukocyte Biology

Self Cite

View full text Add to dashboard Cite

show abstract

Purinergic modulation of the immune response to infections

Eberhardt

Bergero

Mariotta

et al. 2022

Purinergic Signalling

Self Cite

View full text Add to dashboard Cite

Infectious diseases are caused by the invasion of pathogenic microorganisms such as fungi, bacteria, viruses, and parasites. After infection, disease progression relies on the complex interplay between the host immune response and the microorganism evasion strategies. The host’s survival depends on its ability to mount an efficient protective anti-microbial response to accomplish pathogen clearance while simultaneously preventing tissue injury by keeping under control the excessive inflammatory process. The purinergic system has the dual function of regulating the immune response and triggering effector antimicrobial mechanisms. This review provides an overview of the current knowledge of the modulation of innate and adaptive immunity driven by the purinergic system during parasitic, bacterial and viral infections.

show abstract

CD73 mitigates hepatic damage in alcoholic steatohepatitis by regulating PI3K/AKT-mediated hepatocyte pyroptosis

Zhu,

Zhang,

et al. 2023

Biochemical Pharmacology

View full text Add to dashboard Cite

Deficiency of CD73 activity promotes protective cardiac immunity against Trypanosoma cruzi infection but permissive environment in visceral adipose tissue

Cited by 9 publications

References 57 publications

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

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

Purinergic modulation of the immune response to infections

CD73 mitigates hepatic damage in alcoholic steatohepatitis by regulating PI3K/AKT-mediated hepatocyte pyroptosis

Contact Info

Product

Resources

About