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 journalArticle

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 languageEnglish (US)
Pages (from-to)7040-7046
Number of pages7
JournalJournal of Immunology
Volume184
Issue number12
DOIs
StatePublished - Jun 15 2010
Externally publishedYes

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Toxoplasma
Parasites
Macrophages
Single Nucleotide Polymorphism
Adenosine Triphosphate
Mycobacterium tuberculosis
Knockout Mice
Tuberculosis
Alleles
Apoptosis
Bacteria

ASJC Scopus subject areas

  • Immunology

Cite this

Lees, M. P., Fuller, S. J., McLeod, R., Boulter, N. R., Miller, C. M., Zakrzewski, A. M., ... 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. DOI: 10.4049/jimmunol.1000012

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.; Smith, Nicholas C.

In: Journal of Immunology, Vol. 184, No. 12, 15.06.2010, p. 7040-7046.

Research output: Contribution to journalArticle

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. DOI: 10.4049/jimmunol.1000012
Lees MP, Fuller SJ, McLeod R, Boulter NR, Miller CM, Zakrzewski AM et al. P2X7 receptor-mediated killing of an intracellular parasite, Toxoplasma gondii, by human and murine macrophages. Journal of Immunology. 2010 Jun 15;184(12):7040-7046. Available from, DOI: 10.4049/jimmunol.1000012

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.; Smith, Nicholas C. / P2X7 receptor-mediated killing of an intracellular parasite, Toxoplasma gondii, by human and murine macrophages.

In: Journal of Immunology, Vol. 184, No. 12, 15.06.2010, p. 7040-7046.

Research output: Contribution to journalArticle

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