The Role of the P2X7 Receptor in Infectious Diseases

Abstract

ATP is an extracellular signal for the immune system, particularly during an inflammatory response. It is sensed by the P2X7 receptor, the expression of which is upregulated by pro-inflammatory cytokines. Activation of the P2X7 receptor opens a cation-specific channel that alters the ionic environment of the cell, activating several pathways, including (i) the inflammasome, leading to production of IL-1β and IL-18; (ii) the stress-activated protein kinase pathway, resulting in apoptosis; (iii) the mitogen-activated protein kinase pathway, leading to generation of reactive oxygen and nitrogen intermediates; and (iv) phospholipase D, stimulating phagosome-lysosome fusion. The P2X7 receptor can initiate host mechanisms to remove pathogens, most particularly those that parasitise macrophages. At the same time, the P2X7 receptor may be subverted by pathogens to modulate host responses. Moreover, recent genetic studies have demonstrated significant associations between susceptibility or resistance to parasites and bacteria, and loss-of-function or gain-of-function polymorphisms in the P2X7 receptor, underscoring its importance in infectious disease.

Extracellular Nucleotide Catabolism by the Group B Streptococcus Ectonucleotidase NudP Increases Bacterial Survival in Blood

“…The NudP* defects in blood and organs appeared only at the later time point of 48 h, suggesting that NudP is dispensable at early time points of infection. Because NudP acts on extracellular nucleotides, it highlights the role of these extracellular nucleotides in modulating host responses to bacterial infections (2,8,14,18,51).…”

“…The function and the subversion of the eATP receptors, the P2X family, during infections are mainly documented for intracellular microbial pathogens (14,51). In contrast, few studies have address the function of eATP/eAdo receptors during infections by extracellular pathogens and hence the biological consequences of modulating the eATP/eADP ratio (14,51).…”

“…The function and the subversion of the eATP receptors, the P2X family, during infections are mainly documented for intracellular microbial pathogens (14,51). In contrast, few studies have address the function of eATP/eAdo receptors during infections by extracellular pathogens and hence the biological consequences of modulating the eATP/eADP ratio (14,51). In mammals, the two main ectonucleotidases, CD39 and CD73, expressed at the surface of immune cells control the eATP/ eAdo ratio, and their inactivation is detrimental to the clearance of polymicrobial infections (13,52).…”

P2X ion channel receptors and inflammation

“…Associations between susceptibility or resistance to parasites and bacteria and loss-or gain-of-function polymorphisms in the P2X7 receptor indicate that it is important in infectious disease [121]. ATP activation of the NLRP3 inflammasome protects mice against bacterial infection [122].…”

Loss of P2X7 nucleotide receptor function leads to abnormal fat distribution in mice

“…Moreover, P2X7 signaling can cause the formation of large nonselective membrane pores and induce dynamic membrane blebbing [12,13]. This receptor plays important roles in chronic pain [14,15], apoptosis [16][17][18], bone remodeling [19][20][21], immune responses [22][23][24][25] and the function of exocrine and endocrine organs [26,27].…”