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

Western Sydney University

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

116 Citations (Scopus)

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 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.

Original language	English
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
Publication status	Published - 2010

Keywords

P2X7 receptor
Toxoplasma gondii
adenosine triphosphate
intracellular pathogens
macrophages
purines
single nucleotide polymorphisms

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.4049/jimmunol.1000012

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Lees, M. P., Fuller, S. J., McLeod, R., Boulter, N. R., Miller, C. M., Zakrzewski, A. M., Mui, E. J., Witola, WI. 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

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

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 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.",

keywords = "P2X7 receptor, Toxoplasma gondii, adenosine triphosphate, intracellular pathogens, macrophages, purines, single nucleotide polymorphisms",

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

year = "2010",

doi = "10.4049/jimmunol.1000012",

language = "English",

volume = "184",

pages = "7040--7046",

journal = "Journal of Immunology",

issn = "0022-1767",

publisher = "American Association of Immunologists",

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Lees, MP, Fuller, SJ, McLeod, R, Boulter, NR, Miller, CM, Zakrzewski, AM, Mui, EJ, Witola, WIH, 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

TY - JOUR

T1 - P2X7 receptor-mediated killing of an intracellular parasite, Toxoplasma gondii, by human and murine macrophages

AU - Lees, Michael P.

AU - Fuller, Stephen J.

AU - McLeod, Rima

AU - Boulter, Nicola R.

AU - Miller, Catherine M.

AU - Zakrzewski, Alana M.

AU - Mui, Ernest J.

AU - Witola, WIlliam H.

AU - Coyne, Jessica J.

AU - Hargrave, Aubrey C.

AU - Jamieson, Sarra E.

AU - Blackwell, Jenefer M.

AU - Wiley, James S.

AU - Smith, Nicholas C.

PY - 2010

Y1 - 2010

N2 - 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 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.

AB - 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 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.

KW - P2X7 receptor

KW - Toxoplasma gondii

KW - adenosine triphosphate

KW - intracellular pathogens

KW - macrophages

KW - purines

KW - single nucleotide polymorphisms

UR - http://handle.westernsydney.edu.au:8081/1959.7/uws:40239

U2 - 10.4049/jimmunol.1000012

DO - 10.4049/jimmunol.1000012

M3 - Article

SN - 0022-1767

VL - 184

SP - 7040

EP - 7046

JO - Journal of Immunology

JF - Journal of Immunology

IS - 12

ER -

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

Abstract

Keywords

UN SDGs

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