Figure 1.
Schematic illustration showing P2X7 receptor protective (angel) and deleterious (demon) effects in immune responses against pathogens. The recognition of pathogen-associated molecular pattern (PAMPs) by Pattern Recognition Receptors (PRRs) can induce ATP release, which activates P2X7 receptor. As a consequence, P2X7 receptor activation induces ATP release—chiefly via pannexin hemichannels—boosting inflammation. (A) At a molecular level (upper panel) P2X7 receptor beneficial effects are mediated by the stimulation of microbicidal mechanisms and production of inflammatory mediators in phagocytic cells, such as ROS, NO, and interleukins. P2X7 receptor acts as a second signal for NLRP3 inflammasome activation and IL-1β release. In addition, at a cellular level (low panel) P2X7 receptor is involved in the activation of effector T cells, and it favors the polarization of T cells into Th17 cells and decreases the suppressive activity and viability of Tregs. (B) On the other hand, P2X7 can act as a demon depending on the type of pathogen, virulence, and severity of infection by inducing an excessive production and release of inflammatory mediators (upper panel) coupled to a high incidence of apoptotic and necrotic cell death due the release of large amounts of ATP (low panel), which results in sustained P2X7 receptor activation, leading to a self-sustained pro-inflammatory deleterious cycle.