Microbes Infect. 2010 Mar 15. [Epub ahead of print]
Activation of the P2X7 receptor triggers the elimination of Toxoplasma gondii tachyzoites from infected macrophages
Corrêa G, da Silva CM, de Abreu Moreira-Souza AC, Vommaro RC, Coutinho-Silva R.
Laboratory of Immunophysiology, Biophysics Institute Carlos Chagas Filho, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, 373. 21941-902 Rio de Janeiro- Brazil; Laboratory of Cellular Ultrastructure Hertha Meyer, Biophysics Institute Carlos Chagas Filho, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, 373. 21941-902 Rio de Janeiro- Brazil.
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. We here 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. Copyright © 2010. Published by Elsevier SAS.
PMID: 20298798 [PubMed - as supplied by publisher]