The role of the P2X₇ receptor in infectious diseases

• Published in: PLoS pathogens Vol. 7; no. 11; p. e1002212
• Main Authors: Miller, Catherine M, Boulter, Nicola R, Fuller, Stephen J, Zakrzewski, Alana M, Lees, Michael P, Saunders, Bernadette M, Wiley, James S, Smith, Nicholas C
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.11.2011; Public Library of Science (PLoS)
• Subjects: Amino acids; Animals; Apoptosis; Bacteria; Bacteria - immunology; Bacterial Infections - immunology; Bacterial Infections - metabolism; Biology; Cytokines; Disease Susceptibility; Humans; Inflammasomes - metabolism; Interleukin-18 - biosynthesis; Interleukin-1beta - biosynthesis; Ion Channels - metabolism; Kinases; Macrophages - metabolism; Mitogen-Activated Protein Kinases - genetics; Mitogen-Activated Protein Kinases - metabolism; Nitric oxide; Parasites; Parasites - immunology; Parasitic Diseases - immunology; Parasitic Diseases - metabolism; Phospholipase D - biosynthesis; Proteins; Reactive Oxygen Species - metabolism; Receptors, Purinergic P2X7 - genetics; Receptors, Purinergic P2X7 - metabolism; Review; Rodents; Signal Transduction; Studies
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1002212

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.