The role of the [P2X.sub.7] receptor in infectious diseases

• Published in: PLoS pathogens 2011-11, Vol.7 (11)
• 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: Article
• Language: English
• Subjects: Adenosine triphosphate; Apoptosis; Care and treatment; Communicable diseases; Disease susceptibility; Physiological aspects; Risk factors
• ISSN: 1553-7366
• 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 [P2X.sub.7] receptor, the expression of which is upregulated by pro-inflammatory cytokines. Activation of the [P2X.sub.7] 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 phagosomelysosome fusion. The [P2X.sub.7] receptor can initiate host mechanisms to remove pathogens, most particularly those that parasitise macrophages. At the same time, the [P2X.sub.7] 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 [P2X.sub.7] receptor, underscoring its importance in infectious disease.