G protein-coupled purinergic P2Y receptors in infectious diseases

The purinergic P2Y receptors comprise eight G-coupled receptor (GPCR) subtypes already identified (P2Y₁, P2Y₂, P2Y₄, P2Y₆, P2Y₁₁, P2Y_12-14). P2Y receptor physiological agonists are extracellular purine and pyrimidine nucleotides such as ATP (Adenosine triphosphate), ADP (Adenosine diphosphate), UTP (Uridine triphosphate), UDP (Uridine diphosphate), and UDP-glucose. These receptors are expressed in almost all cells. P2Y receptors are found in immune cells, such as macrophages, neutrophils, mast cells, dendritic cells, and lymphocytes. P2Y receptors play essential roles in inflammation and are involved in several cell processes, including efferocytosis, phagocytosis, chemotaxis, degranulation, killing pathogens, cytokine production, and platelet aggregation. These processes underpin immune responses against pathogens. Therefore, here we discuss P2Y receptor pharmacology and mechanisms triggered by the activation of these receptors in virus, bacteria, and parasite infections. In addition, we highlight the therapeutical potential of P2Y receptors for developing new pharmacological strategies to modulate inflammation and disease outcomes in pathogen infections.