The P2X7 Receptor and Its Relation to Neglected Tropical Diseases: Focusing on Chagas Disease

Chagas disease, caused by Trypanosoma cruzi, is a neglected tropical disease (NTD) that can lead to severe cardiac complications, including chronic Chagas cardiomyopathy. While NTDs are caused by a variety of pathogens-such as protozoa, bacteria, viruses, and helminths, Chagas disease remains underexplored, particularly regarding host immune responses. In this context, purinergic signaling has gained attention as a relevant pathway in the regulation of both infection and inflammation. Extracellular adenosine triphosphate (ATP), commonly elevated during inflammatory conditions, acts through P2 receptors, with P2X7 standing out for its ability to induce cell death and modulate cytokine release. This study investigates the involvement of the P2X7 receptor in NTDs, with a particular focus on Chagas disease, due to its established association with cardiovascular inflammation and its potential role in T. cruzi infection. Although other NTDs were initially considered, some NTDs were not investigated in detail because of insufficient data linking P2X7 receptor activity to their pathogenesis. Consequently, the analysis concentrated on Chagas disease, where current evidence indicates that P2X7 receptor activation increases proinflammatory cytokine levels and may contribute to disease progression, especially in its cardiac form. Thus, P2X7R emerges as a promising molecular target for therapeutic strategies and may serve as a potential biomarker for identifying early or indeterminate forms of Chagas disease.