The Role of the P2X7 Receptor in Infectious Diseases

PLoS Pathogens

Bernadette M. Saunders¹  James S. Wiley²  Alana M. Zakrzewski³  Catherine M. Miller³  Nicola R. Boulter³  Michael P. Lees³  Stephen J. Fuller⁴  Nicholas C. Smith⁵ 

[1] Centenary Institute of Cancer Medicine & Cell Biology, The University of Sydney, Camperdown, New South Wales, Australia;Florey Neuroscience Institute, The University of Melbourne, Parkville, Victoria, Australia;Institute for the Biotechnology of Infectious Diseases, University of Technology, Sydney, Broadway, New South Wales, Australia;Nepean Clinical School, Nepean Hospital, The University of Sydney, Penrith, New South Wales, Australia;Queensland Tropical Health Alliance, Faculty of Medicine, Health and Molecular Sciences, James Cook University, Smithfield, Cairns, Queensland, Australia

关键词: Intracellular receptors;    Macrophages;    Apoptosis;    Parasitic diseases;    Nitric oxide;    Toxoplasma gondii;    Phospholipases;    Chlamydia infection;   

DOI  :  10.1371/journal.ppat.1002212

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY