Schistosomiasis is a neglected tropical disease. It is related to long-lasting granulomatous fibrosis
and inflammation of target organs, and current sub-optimal pharmacological treatment creates
global public health concerns. Intravascular worms and eggs release antigens and extracellular vesicles
that target host endothelial cells, modulate the immune system, and stimulate the release of damageassociated
molecular patterns (DAMPs). ATP, one of the most studied DAMPs, triggers a cascade of
autocrine and paracrine actions through purinergic P2X and P2Y receptors, which are shaped by ectonucleotidases
(CD39). Both P2 receptor families, and in particular P2Y1, P2Y2, P2Y12, and P2X7 receptors,
have been attracting increasing interest in several inflammatory diseases and drug development.
Current data obtained from the murine model unveiled a CD39-ADP-P2Y1/P2Y12 receptors signaling
pathway linked to the liver and mesenteric exacerbations of schistosomal inflammation. Therefore, we
proposed that members of this purinergic signaling could be putative pharmacological targets to reduce
Keywords: Purinergic signaling, Schistosomiasis, Endothelial cell, Inflammation, Macrophage, Microbiome, Extracellular
vesicle, ATP, P2Y receptor.
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