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Profiling of the perturbed metabolomic state of mouse spleen during acute and chronic toxoplasmosis

BACKGROUND: Toxoplasma gondii, a common opportunistic protozoan, is a leading cause of illness and mortality among immunosuppressed individuals and during congenital infections. Current therapeutic strategies for toxoplasmosis are not fully effective at curtailing disease progression in these cases....

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Autores principales: Chen, Xiao-Qing, Zhou, Chun-Xue, Elsheikha, Hany M., He, Shuai, Hu, Gui-Xue, Zhu, Xing-Quan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5516376/
https://www.ncbi.nlm.nih.gov/pubmed/28720125
http://dx.doi.org/10.1186/s13071-017-2282-6
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author Chen, Xiao-Qing
Zhou, Chun-Xue
Elsheikha, Hany M.
He, Shuai
Hu, Gui-Xue
Zhu, Xing-Quan
author_facet Chen, Xiao-Qing
Zhou, Chun-Xue
Elsheikha, Hany M.
He, Shuai
Hu, Gui-Xue
Zhu, Xing-Quan
author_sort Chen, Xiao-Qing
collection PubMed
description BACKGROUND: Toxoplasma gondii, a common opportunistic protozoan, is a leading cause of illness and mortality among immunosuppressed individuals and during congenital infections. Current therapeutic strategies for toxoplasmosis are not fully effective at curtailing disease progression in these cases. Given the parasite ability to influence host immunity and metabolism, understanding of the metabolic alterations in the host’s immune organs during T. gondii infection may enhance the understanding of the molecular mechanisms that define the pathophysiology of T. gondii infection. METHODS: We investigated the global metabolic changes in the spleen of BALB/c mice at early and late stage of infection with T. gondii using LC-MS/MS-based metabolomics. Multivariate data analysis methods, principal components analysis (PCA) and partial least squares discriminant analysis (PLS-DA), were used to identify metabolites that are influenced by T. gondii infection. RESULTS: Multivariate analyses clearly separated the metabolites of spleen of infected and control mice. A total of 132 differential metabolites were identified, 23 metabolites from acutely infected versus control mice and 109 metabolites from chronically infected versus control mice. Lipids, hormones, lactones, acids, peptides, antibiotics, alkaloids and natural toxins were the most influenced chemical groups. There were 12 shared differential metabolites between acutely infected versus control mice and chronically infected versus control mice, of which 4,4-Dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol was significantly upregulated and ubiquinone-8 was significantly downregulated. Major perturbed metabolic pathways included primary bile acid biosynthesis, steroid hormone biosynthesis, biotin metabolism, and steroid biosynthesis, with arachidonic acid metabolism being the most significantly impacted pathway. These metabolic changes suggest a multifactorial nature of the immunometabolic responses of mouse spleen to T. gondii infection. CONCLUSIONS: This study demonstrated that T. gondii infection can cause significant metabolomic alterations in the spleen of infected mice. These findings provide new insights into the molecular mechanisms that underpin the pathogenesis of T. gondii infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-017-2282-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-55163762017-07-20 Profiling of the perturbed metabolomic state of mouse spleen during acute and chronic toxoplasmosis Chen, Xiao-Qing Zhou, Chun-Xue Elsheikha, Hany M. He, Shuai Hu, Gui-Xue Zhu, Xing-Quan Parasit Vectors Research BACKGROUND: Toxoplasma gondii, a common opportunistic protozoan, is a leading cause of illness and mortality among immunosuppressed individuals and during congenital infections. Current therapeutic strategies for toxoplasmosis are not fully effective at curtailing disease progression in these cases. Given the parasite ability to influence host immunity and metabolism, understanding of the metabolic alterations in the host’s immune organs during T. gondii infection may enhance the understanding of the molecular mechanisms that define the pathophysiology of T. gondii infection. METHODS: We investigated the global metabolic changes in the spleen of BALB/c mice at early and late stage of infection with T. gondii using LC-MS/MS-based metabolomics. Multivariate data analysis methods, principal components analysis (PCA) and partial least squares discriminant analysis (PLS-DA), were used to identify metabolites that are influenced by T. gondii infection. RESULTS: Multivariate analyses clearly separated the metabolites of spleen of infected and control mice. A total of 132 differential metabolites were identified, 23 metabolites from acutely infected versus control mice and 109 metabolites from chronically infected versus control mice. Lipids, hormones, lactones, acids, peptides, antibiotics, alkaloids and natural toxins were the most influenced chemical groups. There were 12 shared differential metabolites between acutely infected versus control mice and chronically infected versus control mice, of which 4,4-Dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol was significantly upregulated and ubiquinone-8 was significantly downregulated. Major perturbed metabolic pathways included primary bile acid biosynthesis, steroid hormone biosynthesis, biotin metabolism, and steroid biosynthesis, with arachidonic acid metabolism being the most significantly impacted pathway. These metabolic changes suggest a multifactorial nature of the immunometabolic responses of mouse spleen to T. gondii infection. CONCLUSIONS: This study demonstrated that T. gondii infection can cause significant metabolomic alterations in the spleen of infected mice. These findings provide new insights into the molecular mechanisms that underpin the pathogenesis of T. gondii infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-017-2282-6) contains supplementary material, which is available to authorized users. BioMed Central 2017-07-18 /pmc/articles/PMC5516376/ /pubmed/28720125 http://dx.doi.org/10.1186/s13071-017-2282-6 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Chen, Xiao-Qing
Zhou, Chun-Xue
Elsheikha, Hany M.
He, Shuai
Hu, Gui-Xue
Zhu, Xing-Quan
Profiling of the perturbed metabolomic state of mouse spleen during acute and chronic toxoplasmosis
title Profiling of the perturbed metabolomic state of mouse spleen during acute and chronic toxoplasmosis
title_full Profiling of the perturbed metabolomic state of mouse spleen during acute and chronic toxoplasmosis
title_fullStr Profiling of the perturbed metabolomic state of mouse spleen during acute and chronic toxoplasmosis
title_full_unstemmed Profiling of the perturbed metabolomic state of mouse spleen during acute and chronic toxoplasmosis
title_short Profiling of the perturbed metabolomic state of mouse spleen during acute and chronic toxoplasmosis
title_sort profiling of the perturbed metabolomic state of mouse spleen during acute and chronic toxoplasmosis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5516376/
https://www.ncbi.nlm.nih.gov/pubmed/28720125
http://dx.doi.org/10.1186/s13071-017-2282-6
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