A loss-of-function polymorphism in the human P2X7 receptor abolishes ATP-mediated killing of mycobacteria |
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Authors: | Saunders Bernadette M Fernando Suran L Sluyter Ronald Britton Warwick J Wiley James S |
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Institution: | Centenary Institute of Cancer Medicine and Cell Biology, Newtown, NSW Australia. b.saunders@centenary.usyd.edu.au |
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Abstract: | Protective immunity to mycobacterial infections requires activation of the antibacterial mechanisms of infected macrophages. It has previously been reported that ATP treatment of mycobacteria-infected macrophages induces apoptosis mediated via the P2X(7) pathway and that this leads to the death of both the host cell and the internalized bacilli. We have recently identified a single nucleotide polymorphism in the P2X7 gene (1513A-->C), with 1-2% prevalence in the homozygous state, which codes for a nonfunctional receptor. IFN-gamma-primed, mycobacteria-infected macrophages from wild-type individuals were incubated with ATP and this induced apoptosis and reduced mycobacterial viability by 90%. Similar treatment of macrophages from individuals homozygous for the 1513C polymorphism failed to induce apoptosis and did not lead to mycobacterial killing via the P2X(7)-mediated pathway. These data demonstrate that a single nucleotide polymorphism in the P2X7 gene can allow survival of mycobacteria within infected host cells. |
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