CCR5 controls immune and metabolic functions during Toxoplasma gondii infection.

CCR5, an important receptor related to cell recruitment and inflammation, is expressed during experimental Toxoplasma gondii infection. However, its role in the immunopathology of toxoplasmosis is not clearly defined yet. Thus, we inoculated WT and CCR5(-/-) mice with a sub lethal dose of the parasi...

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Autores principales:	Giuliano Bonfá, Luciana Benevides, Maria do Carmo Souza, Denise Morais Fonseca, Tiago Wilson Patriarca Mineo, Marcos Antônio Rossi, Neide Maria Silva, João Santana Silva, Cristina Ribeiro de Barros Cardoso
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d6da1f05983146428c208647b0792edc
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spelling	oai:doaj.org-article:d6da1f05983146428c208647b0792edc2021-11-25T06:04:54ZCCR5 controls immune and metabolic functions during Toxoplasma gondii infection.1932-620310.1371/journal.pone.0104736https://doaj.org/article/d6da1f05983146428c208647b0792edc2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25119429/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203CCR5, an important receptor related to cell recruitment and inflammation, is expressed during experimental Toxoplasma gondii infection. However, its role in the immunopathology of toxoplasmosis is not clearly defined yet. Thus, we inoculated WT and CCR5(-/-) mice with a sub lethal dose of the parasite by oral route. CCR5(-/-) mice were extremely susceptible to infection, presenting higher parasite load and lower tissue expression of IL-12p40, IFN-γ, TNF, IL-6, iNOS, Foxp3, T-bet, GATA-3 and PPARα. Although both groups presented inflammation in the liver with prominent neutrophil infiltration, CCR5(-/-) mice had extensive tissue damage with hepatocyte vacuolization, steatosis, elevated serum triglycerides and transaminases. PPARα agonist Gemfibrozil improved the vacuolization but did not rescue CCR5(-/-) infected mice from high serum triglycerides levels and enhanced mortality. We also found intense inflammation in the ileum of CCR5(-/-) infected mice, with epithelial ulceration, augmented CD4 and decreased frequency of NK cells in the gut lamina propria. Most interestingly, these findings were accompanied by an outstanding accumulation of neutrophils in the ileum, which seemed to be involved in the gut immunopathology, once the depletion of these cells was accompanied by reduced local damage. Altogether, these data demonstrated that CCR5 is essential to the control of T. gondii infection and to maintain the metabolic, hepatic and intestinal integrity. These findings add novel information on the disease pathogenesis and may be relevant for directing future approaches to the treatment of multi-deregulated diseases.Giuliano BonfáLuciana BenevidesMaria do Carmo SouzaDenise Morais FonsecaTiago Wilson Patriarca MineoMarcos Antônio RossiNeide Maria SilvaJoão Santana SilvaCristina Ribeiro de Barros CardosoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 8, p e104736 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Giuliano Bonfá Luciana Benevides Maria do Carmo Souza Denise Morais Fonseca Tiago Wilson Patriarca Mineo Marcos Antônio Rossi Neide Maria Silva João Santana Silva Cristina Ribeiro de Barros Cardoso CCR5 controls immune and metabolic functions during Toxoplasma gondii infection.
description	CCR5, an important receptor related to cell recruitment and inflammation, is expressed during experimental Toxoplasma gondii infection. However, its role in the immunopathology of toxoplasmosis is not clearly defined yet. Thus, we inoculated WT and CCR5(-/-) mice with a sub lethal dose of the parasite by oral route. CCR5(-/-) mice were extremely susceptible to infection, presenting higher parasite load and lower tissue expression of IL-12p40, IFN-γ, TNF, IL-6, iNOS, Foxp3, T-bet, GATA-3 and PPARα. Although both groups presented inflammation in the liver with prominent neutrophil infiltration, CCR5(-/-) mice had extensive tissue damage with hepatocyte vacuolization, steatosis, elevated serum triglycerides and transaminases. PPARα agonist Gemfibrozil improved the vacuolization but did not rescue CCR5(-/-) infected mice from high serum triglycerides levels and enhanced mortality. We also found intense inflammation in the ileum of CCR5(-/-) infected mice, with epithelial ulceration, augmented CD4 and decreased frequency of NK cells in the gut lamina propria. Most interestingly, these findings were accompanied by an outstanding accumulation of neutrophils in the ileum, which seemed to be involved in the gut immunopathology, once the depletion of these cells was accompanied by reduced local damage. Altogether, these data demonstrated that CCR5 is essential to the control of T. gondii infection and to maintain the metabolic, hepatic and intestinal integrity. These findings add novel information on the disease pathogenesis and may be relevant for directing future approaches to the treatment of multi-deregulated diseases.
format	article
author	Giuliano Bonfá Luciana Benevides Maria do Carmo Souza Denise Morais Fonseca Tiago Wilson Patriarca Mineo Marcos Antônio Rossi Neide Maria Silva João Santana Silva Cristina Ribeiro de Barros Cardoso
author_facet	Giuliano Bonfá Luciana Benevides Maria do Carmo Souza Denise Morais Fonseca Tiago Wilson Patriarca Mineo Marcos Antônio Rossi Neide Maria Silva João Santana Silva Cristina Ribeiro de Barros Cardoso
author_sort	Giuliano Bonfá
title	CCR5 controls immune and metabolic functions during Toxoplasma gondii infection.
title_short	CCR5 controls immune and metabolic functions during Toxoplasma gondii infection.
title_full	CCR5 controls immune and metabolic functions during Toxoplasma gondii infection.
title_fullStr	CCR5 controls immune and metabolic functions during Toxoplasma gondii infection.
title_full_unstemmed	CCR5 controls immune and metabolic functions during Toxoplasma gondii infection.
title_sort	ccr5 controls immune and metabolic functions during toxoplasma gondii infection.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/d6da1f05983146428c208647b0792edc
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CCR5 controls immune and metabolic functions during Toxoplasma gondii infection.

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