Activation of the P2X(7) receptor triggers the elimination of Toxoplasma gondii tachyzoites from infected macrophages

Microbes Infect. 2010 Jun;12(6):497-504. doi: 10.1016/j.micinf.2010.03.004. Epub 2010 Mar 16.


Toxoplasmosis is caused by the protozoan parasite Toxoplasma gondii, which is widespread throughout the world. After active penetration, the parasite is enclosed within a parasitophorous vacuole and survives in the host cell by avoiding, among other mechanisms, lysosomal degradation. A large number of studies have demonstrated the importance of ATP signalling via the P2X(7) receptor, as a component of the inflammatory response against intracellular pathogens. Here we evaluate the effects of extracellular ATP on T. gondii infection of macrophages. ATP treatment inhibits the parasite load and the appearance of large vacuoles in the cytoplasm of intracellular parasites. ROS and NO assays showed that only ROS production is involved with the ATP effects. Immunofluorescence showed colocalization of Lamp1 and SAG1 only after ATP treatment, suggesting the formation of phagolysosomes. The involvement of P2X(7) receptors in T. gondii clearance was confirmed by the use of P2X(7) agonists and antagonists, and by infecting macrophages from P2X(7) receptor-deficient mice. We conclude that parasite elimination might occur following P2X(7) signalling and that novel therapies against intracellular pathogens could take advantage of activation of purinergic signalling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / analogs & derivatives
  • Adenosine Triphosphate / metabolism
  • Animals
  • Antigens, Protozoan / metabolism
  • Female
  • Immunohistochemistry
  • Life Cycle Stages / physiology
  • Lysosome-Associated Membrane Glycoproteins / metabolism
  • Macrophages, Peritoneal / immunology
  • Macrophages, Peritoneal / metabolism*
  • Macrophages, Peritoneal / parasitology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Nitric Oxide / metabolism
  • Protozoan Proteins / metabolism
  • Reactive Oxygen Species / metabolism
  • Receptors, Purinergic P2 / immunology
  • Receptors, Purinergic P2 / metabolism*
  • Receptors, Purinergic P2X7
  • Signal Transduction
  • Toxoplasma / immunology
  • Toxoplasma / metabolism
  • Toxoplasma / physiology*
  • Toxoplasmosis / immunology
  • Toxoplasmosis / parasitology
  • Vacuoles / metabolism
  • Vacuoles / parasitology


  • Antigens, Protozoan
  • Lamp1 protein, mouse
  • Lysosome-Associated Membrane Glycoproteins
  • P2rx7 protein, mouse
  • Protozoan Proteins
  • Reactive Oxygen Species
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2X7
  • SAG1 antigen, Toxoplasma
  • Nitric Oxide
  • 3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate
  • Adenosine Triphosphate