title: 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.
authors.affiliation: Institute for the Biotechnology of Infectious Diseases, University of Technology, Sydney, Broadway, New South Wales, Australia.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Miller
authors.forename: Nicola R
authors.initials: NR
authors.lastname: Boulter
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Fuller
authors.forename: Alana M
authors.initials: AM
authors.lastname: Zakrzewski
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lees
authors.forename: Bernadette M
authors.initials: BM
authors.lastname: Saunders
authors.forename: James S
authors.initials: JS
authors.lastname: Wiley
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Smith
mesh_terms: D000818:Animals; D017209:Apoptosis; D001419:Bacteria / Q000276:immunology; D001424:Bacterial Infections / Q000276:immunology / Q000378:metabolism*; D004198:Disease Susceptibility; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D020382:Interleukin-18 / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000096:biosynthesis; D007473:Ion Channels / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D010271:Parasites / Q000276:immunology; D010272:Parasitic Diseases / Q000276:immunology / Q000378:metabolism*; D010739:Phospholipase D / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D058486:Receptors, Purinergic P2X7 / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D007473:Ion Channels; D017382:Reactive Oxygen Species; D058486:Receptors, Purinergic P2X7; D020928:Mitogen-Activated Protein Kinases; D010739:Phospholipase D
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