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Integrative metabolomics and transcriptomics signatures of clinical tolerance to Plasmodium vivax reveal activation of innate cell immunity and T cell signaling
Almost invariably, humans become ill during primary infections with malaria parasites which is a pathology associated with oxidative stress and perturbations in metabolism. Importantly, repetitive exposure to Plasmodium results in asymptomatic infections, which is a condition defined as clinical tol...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007173/ https://www.ncbi.nlm.nih.gov/pubmed/29698924 http://dx.doi.org/10.1016/j.redox.2018.04.011 |
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author | Gardinassi, Luiz G. Arévalo-Herrera, Myriam Herrera, Sócrates Cordy, Regina J. Tran, ViLinh Smith, Matthew R. Johnson, Michelle S. Chacko, Balu Liu, Ken H. Darley-Usmar, Victor M. Go, Young-Mi Jones, Dean P. Galinski, Mary R. Li, Shuzhao |
author_facet | Gardinassi, Luiz G. Arévalo-Herrera, Myriam Herrera, Sócrates Cordy, Regina J. Tran, ViLinh Smith, Matthew R. Johnson, Michelle S. Chacko, Balu Liu, Ken H. Darley-Usmar, Victor M. Go, Young-Mi Jones, Dean P. Galinski, Mary R. Li, Shuzhao |
author_sort | Gardinassi, Luiz G. |
collection | PubMed |
description | Almost invariably, humans become ill during primary infections with malaria parasites which is a pathology associated with oxidative stress and perturbations in metabolism. Importantly, repetitive exposure to Plasmodium results in asymptomatic infections, which is a condition defined as clinical tolerance. Integration of transcriptomics and metabolomics data provides a powerful way to investigate complex disease processes involving oxidative stress, energy metabolism and immune cell activation. We used metabolomics and transcriptomics to investigate the different clinical outcomes in a P. vivax controlled human malaria infection trial. At baseline, the naïve and semi-immune subjects differed in the expression of interferon related genes, neutrophil and B cell signatures that progressed with distinct kinetics after infection. Metabolomics data indicated differences in amino acid pathways and lipid metabolism between the two groups. Top pathways during the course of infection included methionine and cysteine metabolism, fatty acid metabolism and urea cycle. There is also evidence for the activation of lipoxygenase, cyclooxygenase and non-specific lipid peroxidation products in the semi-immune group. The integration of transcriptomics and metabolomics revealed concerted molecular events triggered by the infection, notably involving platelet activation, innate immunity and T cell signaling. Additional experiment confirmed that the metabolites associated with platelet activation genes were indeed enriched in the platelet metabolome. |
format | Online Article Text |
id | pubmed-6007173 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-60071732018-06-20 Integrative metabolomics and transcriptomics signatures of clinical tolerance to Plasmodium vivax reveal activation of innate cell immunity and T cell signaling Gardinassi, Luiz G. Arévalo-Herrera, Myriam Herrera, Sócrates Cordy, Regina J. Tran, ViLinh Smith, Matthew R. Johnson, Michelle S. Chacko, Balu Liu, Ken H. Darley-Usmar, Victor M. Go, Young-Mi Jones, Dean P. Galinski, Mary R. Li, Shuzhao Redox Biol Research Paper Almost invariably, humans become ill during primary infections with malaria parasites which is a pathology associated with oxidative stress and perturbations in metabolism. Importantly, repetitive exposure to Plasmodium results in asymptomatic infections, which is a condition defined as clinical tolerance. Integration of transcriptomics and metabolomics data provides a powerful way to investigate complex disease processes involving oxidative stress, energy metabolism and immune cell activation. We used metabolomics and transcriptomics to investigate the different clinical outcomes in a P. vivax controlled human malaria infection trial. At baseline, the naïve and semi-immune subjects differed in the expression of interferon related genes, neutrophil and B cell signatures that progressed with distinct kinetics after infection. Metabolomics data indicated differences in amino acid pathways and lipid metabolism between the two groups. Top pathways during the course of infection included methionine and cysteine metabolism, fatty acid metabolism and urea cycle. There is also evidence for the activation of lipoxygenase, cyclooxygenase and non-specific lipid peroxidation products in the semi-immune group. The integration of transcriptomics and metabolomics revealed concerted molecular events triggered by the infection, notably involving platelet activation, innate immunity and T cell signaling. Additional experiment confirmed that the metabolites associated with platelet activation genes were indeed enriched in the platelet metabolome. Elsevier 2018-04-11 /pmc/articles/PMC6007173/ /pubmed/29698924 http://dx.doi.org/10.1016/j.redox.2018.04.011 Text en © 2018 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Paper Gardinassi, Luiz G. Arévalo-Herrera, Myriam Herrera, Sócrates Cordy, Regina J. Tran, ViLinh Smith, Matthew R. Johnson, Michelle S. Chacko, Balu Liu, Ken H. Darley-Usmar, Victor M. Go, Young-Mi Jones, Dean P. Galinski, Mary R. Li, Shuzhao Integrative metabolomics and transcriptomics signatures of clinical tolerance to Plasmodium vivax reveal activation of innate cell immunity and T cell signaling |
title | Integrative metabolomics and transcriptomics signatures of clinical tolerance to Plasmodium vivax reveal activation of innate cell immunity and T cell signaling |
title_full | Integrative metabolomics and transcriptomics signatures of clinical tolerance to Plasmodium vivax reveal activation of innate cell immunity and T cell signaling |
title_fullStr | Integrative metabolomics and transcriptomics signatures of clinical tolerance to Plasmodium vivax reveal activation of innate cell immunity and T cell signaling |
title_full_unstemmed | Integrative metabolomics and transcriptomics signatures of clinical tolerance to Plasmodium vivax reveal activation of innate cell immunity and T cell signaling |
title_short | Integrative metabolomics and transcriptomics signatures of clinical tolerance to Plasmodium vivax reveal activation of innate cell immunity and T cell signaling |
title_sort | integrative metabolomics and transcriptomics signatures of clinical tolerance to plasmodium vivax reveal activation of innate cell immunity and t cell signaling |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007173/ https://www.ncbi.nlm.nih.gov/pubmed/29698924 http://dx.doi.org/10.1016/j.redox.2018.04.011 |
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