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 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.
authors.affiliation: Institute for the Biotechnology of Infectious Diseases, University of Technology, Sydney, Broadway, NSW, Australia.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lees
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Fuller
authors.forename: Rima
authors.initials: R
authors.lastname: McLeod
authors.forename: Nicola R
authors.initials: NR
authors.lastname: Boulter
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Miller
authors.forename: Alana M
authors.initials: AM
authors.lastname: Zakrzewski
authors.forename: Ernest J
authors.initials: EJ
authors.lastname: Mui
authors.forename: William H
authors.initials: WH
authors.lastname: Witola
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Coyne
authors.forename: Aubrey C
authors.initials: AC
authors.lastname: Hargrave
authors.forename: Sarra E
authors.initials: SE
authors.lastname: Jamieson
authors.forename: Jenefer M
authors.initials: JM
authors.lastname: Blackwell
authors.forename: James S
authors.initials: JS
authors.lastname: Wiley
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Smith
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D002469:Cell Separation; D005434:Flow Cytometry; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000096:biosynthesis / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D018048:Receptors, Purinergic P2 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D058486:Receptors, Purinergic P2X7; D014122:Toxoplasma; D014123:Toxoplasmosis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D014124:Toxoplasmosis, Animal / Q000235:genetics / Q000378:metabolism
chemical_list: C546468:P2RX7 protein, human; C546469:P2rx7 protein, mouse; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D009569:Nitric Oxide