Pyrimidinergic Receptor Activation Controls Toxoplasma gondii Infection in Macrophages

dc.creatorSouza, Aline Cristina Abreu Moreira
dc.creatorMarinho, Ygor
dc.creatorCorrea, Gladys
dc.creatorSantoro, Giani França
dc.creatorCoutinho, Claudia Mara Lara Melo
dc.creatorVommaro, Rossiane Claudia
dc.creatorSilva, Robson Coutinho
dc.date2016-05-10T13:37:41Z
dc.date2016-05-10T13:37:41Z
dc.date2015
dc.date.accessioned2023-09-26T22:09:07Z
dc.date.available2023-09-26T22:09:07Z
dc.identifierSOUZA, Aline Cristina Abreu Moreira; et al. Pyrimidinergic Receptor Activation Controls Toxoplasma gondii Infection in Macrophages. Plos One, v.10, n.7, e0133502, 23p, Jul. 2015.
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/14144
dc.identifier10.1371/journal. pone.0133502
dc.identifier1932-6203
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8875449
dc.descriptionInfection by the protozoan parasite Toxoplasma gondii is highly prevalent worldwide and may have serious clinical manifestations in immunocompromised patients. T. gondii is an obligate intracellular parasite that infects almost any cell type in mammalian hosts, including immune cells. The immune cells express purinergic P2 receptors in their membrane – subdivided into P2Y and P2X subfamilies - whose activation is important for infection control. Here, we examined the effect of treatment with UTP and UDP in mouse peritoneal macrophages infected with T. gondii tachyzoites. Treatment with these nucleotides reduced parasitic load by 90%, but did not increase the levels of the inflammatory mediators NO and ROS, nor did it modulate host cell death by apoptosis or necrosis. On the other hand, UTP and UDP treatments induced early egress of tachyzoites from infected macrophages, in a Ca2+-dependent manner, as shown by scanning electron microscopy analysis, and videomicroscopy. In subsequent infections, prematurely egressed parasites had reduced infectivity, and could neither replicate nor inhibit the fusion of lysosomes to the parasitophorous vacuole. The use of selective agonists and antagonists of the receptor subtypes P2Y2 and P2Y4 and P2Y6 showed that premature parasite egress may be mediated by the activation of these receptor subtypes. Our results suggest that the activity of P2Y host cell receptors controls T. gondii infection in macrophages, highlighting the importance of pyrimidinergic signaling for innate immune system response against infection. Finally the P2Y receptors should be considered as new target for the development of drugs against T. gondii infection.
dc.formatapplication/pdf
dc.languageeng
dc.publisherPublic Library of Science
dc.rightsopen access
dc.subjectToxoplasma gondii
dc.subjectMacrophages
dc.subjectInfection
dc.subjectPyrimidinergic Receptor
dc.subjectP2Y receptors
dc.subjectToxoplasma
dc.subjectMacrófagos
dc.subjectInfecção
dc.subjectReceptores
dc.subjectParasitos
dc.titlePyrimidinergic Receptor Activation Controls Toxoplasma gondii Infection in Macrophages
dc.typeArticle


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