P2X7 Receptor-Mediated Killing of an Intracellular Parasite,Toxoplasma gondii, by Human and Murine Macrophages | Zendy

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

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P2X7 Receptor-Mediated Killing of an Intracellular Parasite,Toxoplasma gondii, by Human and Murine Macrophages

Author(s) -

Michael P. Lees,

Stephen J. Fuller,

Rima McLeod,

Nicola R. Boulter,

Catherine Miller,

Alana M. Zakrzewski,

Ernest Mui,

William H. Witola,

Jessica J. Coyne,

Aubrey Hargrave,

Sarra E. Jamieson,

Jenefer M. Blackwell,

James S. Wiley,

Nicholas C. Smith

Publication year - 2010

Publication title -

the journal of immunology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.737

H-Index - 372

eISSN - 1550-6606

pISSN - 0022-1767

DOI - 10.4049/jimmunol.1000012

Subject(s) - toxoplasma gondii , intracellular parasite , intracellular , biology , extracellular , macrophage , microbiology and biotechnology , receptor , wild type , mycobacterium tuberculosis , virology , tuberculosis , immunology , gene , genetics , antibody , in vitro , mutant , medicine , pathology

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.

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