Activation of the P2X₇ receptor triggers the elimination of Toxoplasma gondii tachyzoites from infected macrophages

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• 作者：Gladys Corr&#xea ; a ; Camila Marques da Silva ; Aline Cristina de Abreu Moreira-Souza ; Rossiane Claudia Vommaro ; Robson Coutinho-Silva
• 关键词：ATP ; P2X₇ ; Toxoplasma gondii ; Purinergic signalling ; Intracellular parasite
• 刊名：Microbes and Infection
• 出版年：2010
• 出版时间：June 2010
• 年：2010
• 卷：12
• 期：6
• 页码：497-504
• 全文大小：1673 K

文摘

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 P2X₇ 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 P2X₇ receptors in T. gondii clearance was confirmed by the use of P2X₇ agonists and antagonists, and by infecting macrophages from P2X₇ receptor-deficient mice. We conclude that parasite elimination might occur following P2X₇ signalling and that novel therapies against intracellular pathogens could take advantage of activation of purinergic signalling.