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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25119429/pdf/?tool=EBI |
| _version_ | 1819240906794991616 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-23T14:15:28Z |
| format | Article |
| id | doaj.art-d6da1f05983146428c208647b0792edc |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T14:15:28Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-d6da1f05983146428c208647b0792edc2022-12-21T17:43:56ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0198e10473610.1371/journal.pone.0104736CCR5 controls immune and metabolic functions during Toxoplasma gondii infection.Giuliano BonfáLuciana BenevidesMaria do Carmo SouzaDenise Morais FonsecaTiago Wilson Patriarca MineoMarcos Antônio RossiNeide Maria SilvaJoão Santana SilvaCristina Ribeiro de Barros CardosoCCR5, 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25119429/pdf/?tool=EBI |
| spellingShingle | 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. PLoS ONE |
| title | 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_short | CCR5 controls immune and metabolic functions during Toxoplasma gondii infection. |
| title_sort | ccr5 controls immune and metabolic functions during toxoplasma gondii infection |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25119429/pdf/?tool=EBI |
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