P2X7 receptor-mediated killing of an intracellular parasite, Toxoplasma gondii, by human and murine macrophages

Lees, Michael P., Fuller, Stephen J., McLeod, Rima, Boulter, Nicola R., Miller, Catherine M., Zakrzewski, Alana M., Mui, Ernest J., Witola, William H., Coyne, Jessica J., Hargrave, Aubrey C., Jamieson, Sarra E., Blackwell, Jenefer M., Wiley, James S., and Smith, Nicholas C. (2010) P2X7 receptor-mediated killing of an intracellular parasite, Toxoplasma gondii, by human and murine macrophages. The Journal of Immunology, 184 (12). pp. 7040-7046.

[img] PDF (Published Version) - Published Version
Restricted to Repository staff only

View at Publisher Website: http://dx.doi.org/10.4049/jimmunol.10000...
 
79
5


Abstract

The P2X₇R is highly expressed on the macrophage cell surface, and activation of infected cells by extracellular ATP has been shown to kill intracellular bacteria and parasites. Furthermore, single nucleotide polymorphisms that decrease receptor function reduce the ability of human macrophages to kill Mycobacterium tuberculosis and are associated with extrapulmonary tuberculosis. In this study, we show that macrophages from people with the 1513C (rs3751143, NM_002562.4:c.1487A>C) loss-of-function P2X₇R single nucleotide polymorphism are less effective in killing intracellular Toxoplasma gondii after exposure to ATP compared with macrophages from people with the 1513A wild-type allele. Supporting a P2X7R-specific effect on T. gondii, macrophages from P2X₇R knockout mice (P2X₇R^−/−) are unable to kill T. gondii as effectively as macrophages from wild-type mice. We show that P2X₇R-mediated T. gondii killing occurs in parallel with host cell apoptosis and is independent of NO production.

Item ID: 26362
Item Type: Article (Research - C1)
ISSN: 1550-6606
Funders: Australian Research Council (ARC)
Projects and Grants: DP666515
Date Deposited: 13 Jun 2013 05:14
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110803 Medical Parasitology @ 70%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110707 Innate Immunity @ 30%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 40%
97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 40%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 20%
Downloads: Total: 5
More Statistics

Actions (Repository Staff Only)

Item Control Page Item Control Page