PLoS Pathogens (Nov 2011)

The role of the P2X₇ receptor in infectious diseases.

  • Catherine M Miller,
  • Nicola R Boulter,
  • Stephen J Fuller,
  • Alana M Zakrzewski,
  • Michael P Lees,
  • Bernadette M Saunders,
  • James S Wiley,
  • Nicholas C Smith

DOI
https://doi.org/10.1371/journal.ppat.1002212
Journal volume & issue
Vol. 7, no. 11
p. e1002212

Abstract

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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.