The role of p2x7 receptor in infectious inflammatory diseases and the influence of ectonucleotidases

W hen the body is challenged by pathogens during infections, the first-line defense for the host is provided by the innate immune system which encompasses various cell types such as macrophages, dendritic cells (DCs), and natural killer (NK) cells. These cells express the so-called pattern recognition receptors (PRRs) including Toll-Like receptors (TLRs), NOD-like receptors (NLRs), and RIG-I-like receptors (RLRs) on their surface and can recognize pathogen-associated molecular patterns (PAMPs) of bacterial and viral pathogens. After recognition of PAMPs by PRRs, diverse signaling pathways can be initiated resulting in the induction of pro-and anti-inflammatory cytokines and chemokines, which are essential for the host defense. Current literature evidence suggests a relationship between the cellular immune reaction and its regulation by cellular stress pathways, often activated in infections and chronic diseases as survival mechanisms activated by cells in response to stressful stimuli, as reviewed elsewhere. n this context, some endogenous intracellular molecules from the host can be secreted into the extracellular environment and they control the function of immune cells under pathological situations. During inflammatory conditions, extracellular ATP, which is classically associated with cellular energy metabolism, is often reported to be released passively following cellular stress or cell death. Extracellular ATP and the related purine and pyrimidine nucleotides exert their functions via signaling through membrane-bound purinergic P2 receptors. These receptors are widely expressed throughout the body on various immune and non-immune