P2X<inf>7</inf> receptor-mediated killing of an intracellular parasite, Toxoplasma gondii, by human and murine macrophages

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

P2X<inf>7</inf> receptor-mediated killing of an intracellular parasite, Toxoplasma gondii, by human and murine macrophages

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

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Publication Type:: Journal Article
Citation:: Journal of Immunology, 2010, 184 (12), pp. 7040 - 7046
Issue Date:: 2010-06-15

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Field	Value	Language
dc.contributor.author	Lees, MP	en_US
dc.contributor.author	Fuller, SJ	en_US
dc.contributor.author	McLeod, R	en_US
dc.contributor.author	Boulter, NR	en_US
dc.contributor.author	Miller, CM https://orcid.org/0000-0001-6071-5102	en_US
dc.contributor.author	Zakrzewski, AM	en_US
dc.contributor.author	Mui, EJ	en_US
dc.contributor.author	Witola, WH	en_US
dc.contributor.author	Coyne, JJ	en_US
dc.contributor.author	Hargrave, AC	en_US
dc.contributor.author	Jamieson, SE	en_US
dc.contributor.author	Blackwell, JM	en_US
dc.contributor.author	Wiley, JS	en_US
dc.contributor.author	Smith, NC https://orcid.org/0000-0002-7467-1451	en_US
dc.date.issued	2010-06-15	en_US
dc.identifier.citation	Journal of Immunology, 2010, 184 (12), pp. 7040 - 7046	en_US
dc.identifier.issn	0022-1767	en_US
dc.identifier.uri	http://hdl.handle.net/10453/17140
dc.description.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. Copyright © 2010 by The American Association of Immunologists, Inc.	en_US
dc.relation.ispartof	Journal of Immunology	en_US
dc.relation.isbasedon	10.4049/jimmunol.1000012	en_US
dc.subject.classification	Immunology	en_US
dc.subject.mesh	Macrophages	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Knockout	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Toxoplasma	en_US
dc.subject.mesh	Toxoplasmosis, Animal	en_US
dc.subject.mesh	Toxoplasmosis	en_US
dc.subject.mesh	Nitric Oxide	en_US
dc.subject.mesh	Receptors, Purinergic P2	en_US
dc.subject.mesh	Flow Cytometry	en_US
dc.subject.mesh	Cell Separation	en_US
dc.subject.mesh	Apoptosis	en_US
dc.subject.mesh	Polymorphism, Single Nucleotide	en_US
dc.subject.mesh	Receptors, Purinergic P2X7	en_US
dc.title	P2X<inf>7</inf> receptor-mediated killing of an intracellular parasite, Toxoplasma gondii, by human and murine macrophages	en_US
dc.type	Journal Article
utslib.citation.volume	12	en_US
utslib.citation.volume	184	en_US
utslib.for	1107 Immunology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access
pubs.issue	12	en_US
pubs.publication-status	Published	en_US
pubs.volume	184	en_US

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. Copyright © 2010 by The American Association of Immunologists, Inc.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/17140