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

Michael P. Lees; Stephen J. Fuller; Rima McLeod; Nicola R. Boulter; Catherine M. Miller; Alana M. Zakrzewski; Ernest J. Mui; William H. Witola; Jessica J. Coyne; Aubrey C. Hargrave; Sarra E. Jamieson; Jenefer M. Blackwell; James S. Wiley; Nicholas C. Smith

doi:10.4049/jimmunol.1000012

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

Michael P. Lees, Stephen J. Fuller, Rima McLeod, Nicola R. Boulter, Catherine M. Miller, Alana M. Zakrzewski, Ernest J. Mui, William H. Witola, Jessica J. Coyne, Aubrey C. Hargrave, Sarra E. Jamieson, Jenefer M. Blackwell, James S. Wiley, Nicholas C. Smith

Research output: Contribution to journal › Article › peer-review

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 P2X ₇R 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 P2X ₇R-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 P2X ₇R-mediated T. gondii killing occurs in parallel with host cell apoptosis and is independent of NO production.

Original language	English (US)
Pages (from-to)	7040-7046
Number of pages	7
Journal	Journal of Immunology
Volume	184
Issue number	12
DOIs	https://doi.org/10.4049/jimmunol.1000012
State	Published - Jun 15 2010
Externally published	Yes

ASJC Scopus subject areas

Immunology and Allergy
Immunology

Online availability

10.4049/jimmunol.1000012

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Cite this

Lees, M. P., Fuller, S. J., McLeod, R., Boulter, N. R., Miller, C. M., Zakrzewski, A. M., Mui, E. J., Witola, W. H., Coyne, J. J., Hargrave, A. C., Jamieson, S. E., Blackwell, J. M., Wiley, J. S., & Smith, N. C. (2010). P2X₇ receptor-mediated killing of an intracellular parasite, Toxoplasma gondii, by human and murine macrophages. Journal of Immunology, 184(12), 7040-7046. https://doi.org/10.4049/jimmunol.1000012

Lees, MP, Fuller, SJ, McLeod, R, Boulter, NR, Miller, CM, Zakrzewski, AM, Mui, EJ, Witola, WH, Coyne, JJ, Hargrave, AC, Jamieson, SE, Blackwell, JM, Wiley, JS & Smith, NC 2010, 'P2X₇ receptor-mediated killing of an intracellular parasite, Toxoplasma gondii, by human and murine macrophages', Journal of Immunology, vol. 184, no. 12, pp. 7040-7046. https://doi.org/10.4049/jimmunol.1000012

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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 P2X 7R 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 P2X 7R-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 P2X 7R-mediated T. gondii killing occurs in parallel with host cell apoptosis and is independent of NO production.",

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