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Pyrimidinergic Receptor Activation Controls Toxoplasma gondii Infection in Macrophages

Infection 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 cel...

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Autores principales: Moreira-Souza, Aline Cristina Abreu, Marinho, Ygor, Correa, Gladys, Santoro, Giani França, Coutinho, Claudia Mara Lara Melo, Vommaro, Rossiane Claudia, Coutinho-Silva, Robson
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4507979/
https://www.ncbi.nlm.nih.gov/pubmed/26192447
http://dx.doi.org/10.1371/journal.pone.0133502
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author Moreira-Souza, Aline Cristina Abreu
Marinho, Ygor
Correa, Gladys
Santoro, Giani França
Coutinho, Claudia Mara Lara Melo
Vommaro, Rossiane Claudia
Coutinho-Silva, Robson
author_facet Moreira-Souza, Aline Cristina Abreu
Marinho, Ygor
Correa, Gladys
Santoro, Giani França
Coutinho, Claudia Mara Lara Melo
Vommaro, Rossiane Claudia
Coutinho-Silva, Robson
author_sort Moreira-Souza, Aline Cristina Abreu
collection PubMed
description Infection 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 Ca(2+)-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 P2Y(2) and P2Y(4) and P2Y(6) 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.
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spelling pubmed-45079792015-07-24 Pyrimidinergic Receptor Activation Controls Toxoplasma gondii Infection in Macrophages Moreira-Souza, Aline Cristina Abreu Marinho, Ygor Correa, Gladys Santoro, Giani França Coutinho, Claudia Mara Lara Melo Vommaro, Rossiane Claudia Coutinho-Silva, Robson PLoS One Research Article Infection 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 Ca(2+)-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 P2Y(2) and P2Y(4) and P2Y(6) 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. Public Library of Science 2015-07-20 /pmc/articles/PMC4507979/ /pubmed/26192447 http://dx.doi.org/10.1371/journal.pone.0133502 Text en © 2015 Moreira-Souza et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Moreira-Souza, Aline Cristina Abreu
Marinho, Ygor
Correa, Gladys
Santoro, Giani França
Coutinho, Claudia Mara Lara Melo
Vommaro, Rossiane Claudia
Coutinho-Silva, Robson
Pyrimidinergic Receptor Activation Controls Toxoplasma gondii Infection in Macrophages
title Pyrimidinergic Receptor Activation Controls Toxoplasma gondii Infection in Macrophages
title_full Pyrimidinergic Receptor Activation Controls Toxoplasma gondii Infection in Macrophages
title_fullStr Pyrimidinergic Receptor Activation Controls Toxoplasma gondii Infection in Macrophages
title_full_unstemmed Pyrimidinergic Receptor Activation Controls Toxoplasma gondii Infection in Macrophages
title_short Pyrimidinergic Receptor Activation Controls Toxoplasma gondii Infection in Macrophages
title_sort pyrimidinergic receptor activation controls toxoplasma gondii infection in macrophages
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4507979/
https://www.ncbi.nlm.nih.gov/pubmed/26192447
http://dx.doi.org/10.1371/journal.pone.0133502
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