Mutation in Human P2X7 Receptor Gene Enables Mycobacterial Survival

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A mutation in the human P2X7 receptor gene has been found to enable mycobacterial survival in infected macrophages. This genetic variation, which affects the functioning of the P2X7 receptor pathway, can lead to a lack of apoptosis in infected cells, allowing mycobacteria to survive and thrive. Researchers in Australia have identified a single nucleotide polymorphism in the P2X7 gene that codes for a nonfunctional receptor, which can hinder the ability of macrophages to kill mycobacteria.

Key Takeaways:

  • A mutation in the human P2X7 receptor gene can enable mycobacterial survival in infected macrophages.
  • The mutation affects the functioning of the P2X7 receptor pathway, leading to a lack of apoptosis in infected cells.
  • Researchers identified a single nucleotide polymorphism in the P2X7 gene that codes for a nonfunctional receptor.
  • The polymorphism is present in 1-2% of individuals in the homozygous state.
  • IFN-gamma-primed, mycobacteria-infected macrophages from wild-type individuals exhibited 90% reduction in mycobacterial viability after treatment with ATP.
  • Macrophages from individuals homozygous for the 1513C polymorphism failed to induce apoptosis and did not lead to mycobacterial killing via the P2X7-mediated pathway.

Statistics:

  • 1-2% prevalence of the homozygous state of the 1513A--C polymorphism in the general population.
  • 90% reduction in mycobacterial viability after ATP treatment in wild-type individuals.
  • 10% survival of mycobacteria in macrophages from individuals homozygous for the 1513C polymorphism.

Sources:

  • NewsRx.com & NewsRx.net

(Journal of Immunology: A loss-of-function polymorphism in the human P2X(7) receptor abolishes ATP-mediated killing of mycobacteria. J Immunol, 2003;171(10):5442-5446)