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.
Highlights
In addition to its role in cellular metabolism, the purine nucleotide ATP acts as an important extracellular messenger in a range of physiological processes, including synaptic transmissions, taste, bone formation/resorption, male fertility, blood pressure regulation, and inflammation [1,2,3]
Its effects are mediated through activation of purinergic receptors such as the P1 adenosine and the P2 nucleotide receptors [4]
Evidence for P2X7 receptor involvement in mycobacterial killing comes from studies showing that loss-of-function polymorphisms in the human P2X7 receptor gene lead to increased susceptibility to M. tuberculosis
Summary
In addition to its role in cellular metabolism, the purine nucleotide ATP acts as an important extracellular messenger in a range of physiological processes, including synaptic transmissions, taste, bone formation/resorption, male fertility, blood pressure regulation, and inflammation [1,2,3]. A number of change-of-function polymorphisms, most of which render the receptor inactive or with reduced function, have been noted in the human population (Table 1) [25,26,27,28,29,30,31,32], and genetic association studies have uncovered links between some of these polymorphisms and resistance/ susceptibility to mood disorders, bone diseases, and, most infectious disease [26] It should be noted, that immune cells express P2Y receptors, such as P2Y2, which are activated by inflammatory cytokines and, so, may contribute to the regulation of inflammation [5]. Evidence for P2X7 receptor involvement in mycobacterial killing comes from studies showing that loss-of-function polymorphisms in the human P2X7 receptor gene lead to increased susceptibility to M. tuberculosis. Amino Acid Change Produces null allele Val-76.Ala Gly-150.Arg His-155.Tyr His-270.Arg Arg-276.His Arg-307.Gln
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
