Toxoplasma Modulates Signature Pathways of Human Epilepsy, Neurodegeneration & Cancer

One third of humans are infected lifelong with the brain-dwelling, protozoan parasite, Toxoplasma gondii. Approximately fifteen million of these have congenital toxoplasmosis. Although neurobehavioral disease is associated with seropositivity, causality is unproven. To better understand what this pa...

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Autores principales: Ngô, Huân M., Zhou, Ying, Lorenzi, Hernan, Wang, Kai, Kim, Taek-Kyun, Zhou, Yong, El Bissati, Kamal, Mui, Ernest, Fraczek, Laura, Rajagopala, Seesandra V., Roberts, Craig W., Henriquez, Fiona L., Montpetit, Alexandre, Blackwell, Jenefer M., Jamieson, Sarra E., Wheeler, Kelsey, Begeman, Ian J., Naranjo-Galvis, Carlos, Alliey-Rodriguez, Ney, Davis, Roderick G., Soroceanu, Liliana, Cobbs, Charles, Steindler, Dennis A., Boyer, Kenneth, Noble, A. Gwendolyn, Swisher, Charles N., Heydemann, Peter T., Rabiah, Peter, Withers, Shawn, Soteropoulos, Patricia, Hood, Leroy, McLeod, Rima
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5597608/
https://www.ncbi.nlm.nih.gov/pubmed/28904337
http://dx.doi.org/10.1038/s41598-017-10675-6
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author Ngô, Huân M.
Zhou, Ying
Lorenzi, Hernan
Wang, Kai
Kim, Taek-Kyun
Zhou, Yong
El Bissati, Kamal
Mui, Ernest
Fraczek, Laura
Rajagopala, Seesandra V.
Roberts, Craig W.
Henriquez, Fiona L.
Montpetit, Alexandre
Blackwell, Jenefer M.
Jamieson, Sarra E.
Wheeler, Kelsey
Begeman, Ian J.
Naranjo-Galvis, Carlos
Alliey-Rodriguez, Ney
Davis, Roderick G.
Soroceanu, Liliana
Cobbs, Charles
Steindler, Dennis A.
Boyer, Kenneth
Noble, A. Gwendolyn
Swisher, Charles N.
Heydemann, Peter T.
Rabiah, Peter
Withers, Shawn
Soteropoulos, Patricia
Hood, Leroy
McLeod, Rima
author_facet Ngô, Huân M.
Zhou, Ying
Lorenzi, Hernan
Wang, Kai
Kim, Taek-Kyun
Zhou, Yong
El Bissati, Kamal
Mui, Ernest
Fraczek, Laura
Rajagopala, Seesandra V.
Roberts, Craig W.
Henriquez, Fiona L.
Montpetit, Alexandre
Blackwell, Jenefer M.
Jamieson, Sarra E.
Wheeler, Kelsey
Begeman, Ian J.
Naranjo-Galvis, Carlos
Alliey-Rodriguez, Ney
Davis, Roderick G.
Soroceanu, Liliana
Cobbs, Charles
Steindler, Dennis A.
Boyer, Kenneth
Noble, A. Gwendolyn
Swisher, Charles N.
Heydemann, Peter T.
Rabiah, Peter
Withers, Shawn
Soteropoulos, Patricia
Hood, Leroy
McLeod, Rima
author_sort Ngô, Huân M.
collection PubMed
description One third of humans are infected lifelong with the brain-dwelling, protozoan parasite, Toxoplasma gondii. Approximately fifteen million of these have congenital toxoplasmosis. Although neurobehavioral disease is associated with seropositivity, causality is unproven. To better understand what this parasite does to human brains, we performed a comprehensive systems analysis of the infected brain: We identified susceptibility genes for congenital toxoplasmosis in our cohort of infected humans and found these genes are expressed in human brain. Transcriptomic and quantitative proteomic analyses of infected human, primary, neuronal stem and monocytic cells revealed effects on neurodevelopment and plasticity in neural, immune, and endocrine networks. These findings were supported by identification of protein and miRNA biomarkers in sera of ill children reflecting brain damage and T. gondii infection. These data were deconvoluted using three systems biology approaches: “Orbital-deconvolution” elucidated upstream, regulatory pathways interconnecting human susceptibility genes, biomarkers, proteomes, and transcriptomes. “Cluster-deconvolution” revealed visual protein-protein interaction clusters involved in processes affecting brain functions and circuitry, including lipid metabolism, leukocyte migration and olfaction. Finally, “disease-deconvolution” identified associations between the parasite-brain interactions and epilepsy, movement disorders, Alzheimer’s disease, and cancer. This “reconstruction-deconvolution” logic provides templates of progenitor cells’ potentiating effects, and components affecting human brain parasitism and diseases.
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spelling pubmed-55976082017-09-15 Toxoplasma Modulates Signature Pathways of Human Epilepsy, Neurodegeneration & Cancer Ngô, Huân M. Zhou, Ying Lorenzi, Hernan Wang, Kai Kim, Taek-Kyun Zhou, Yong El Bissati, Kamal Mui, Ernest Fraczek, Laura Rajagopala, Seesandra V. Roberts, Craig W. Henriquez, Fiona L. Montpetit, Alexandre Blackwell, Jenefer M. Jamieson, Sarra E. Wheeler, Kelsey Begeman, Ian J. Naranjo-Galvis, Carlos Alliey-Rodriguez, Ney Davis, Roderick G. Soroceanu, Liliana Cobbs, Charles Steindler, Dennis A. Boyer, Kenneth Noble, A. Gwendolyn Swisher, Charles N. Heydemann, Peter T. Rabiah, Peter Withers, Shawn Soteropoulos, Patricia Hood, Leroy McLeod, Rima Sci Rep Article One third of humans are infected lifelong with the brain-dwelling, protozoan parasite, Toxoplasma gondii. Approximately fifteen million of these have congenital toxoplasmosis. Although neurobehavioral disease is associated with seropositivity, causality is unproven. To better understand what this parasite does to human brains, we performed a comprehensive systems analysis of the infected brain: We identified susceptibility genes for congenital toxoplasmosis in our cohort of infected humans and found these genes are expressed in human brain. Transcriptomic and quantitative proteomic analyses of infected human, primary, neuronal stem and monocytic cells revealed effects on neurodevelopment and plasticity in neural, immune, and endocrine networks. These findings were supported by identification of protein and miRNA biomarkers in sera of ill children reflecting brain damage and T. gondii infection. These data were deconvoluted using three systems biology approaches: “Orbital-deconvolution” elucidated upstream, regulatory pathways interconnecting human susceptibility genes, biomarkers, proteomes, and transcriptomes. “Cluster-deconvolution” revealed visual protein-protein interaction clusters involved in processes affecting brain functions and circuitry, including lipid metabolism, leukocyte migration and olfaction. Finally, “disease-deconvolution” identified associations between the parasite-brain interactions and epilepsy, movement disorders, Alzheimer’s disease, and cancer. This “reconstruction-deconvolution” logic provides templates of progenitor cells’ potentiating effects, and components affecting human brain parasitism and diseases. Nature Publishing Group UK 2017-09-13 /pmc/articles/PMC5597608/ /pubmed/28904337 http://dx.doi.org/10.1038/s41598-017-10675-6 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Ngô, Huân M.
Zhou, Ying
Lorenzi, Hernan
Wang, Kai
Kim, Taek-Kyun
Zhou, Yong
El Bissati, Kamal
Mui, Ernest
Fraczek, Laura
Rajagopala, Seesandra V.
Roberts, Craig W.
Henriquez, Fiona L.
Montpetit, Alexandre
Blackwell, Jenefer M.
Jamieson, Sarra E.
Wheeler, Kelsey
Begeman, Ian J.
Naranjo-Galvis, Carlos
Alliey-Rodriguez, Ney
Davis, Roderick G.
Soroceanu, Liliana
Cobbs, Charles
Steindler, Dennis A.
Boyer, Kenneth
Noble, A. Gwendolyn
Swisher, Charles N.
Heydemann, Peter T.
Rabiah, Peter
Withers, Shawn
Soteropoulos, Patricia
Hood, Leroy
McLeod, Rima
Toxoplasma Modulates Signature Pathways of Human Epilepsy, Neurodegeneration & Cancer
title Toxoplasma Modulates Signature Pathways of Human Epilepsy, Neurodegeneration & Cancer
title_full Toxoplasma Modulates Signature Pathways of Human Epilepsy, Neurodegeneration & Cancer
title_fullStr Toxoplasma Modulates Signature Pathways of Human Epilepsy, Neurodegeneration & Cancer
title_full_unstemmed Toxoplasma Modulates Signature Pathways of Human Epilepsy, Neurodegeneration & Cancer
title_short Toxoplasma Modulates Signature Pathways of Human Epilepsy, Neurodegeneration & Cancer
title_sort toxoplasma modulates signature pathways of human epilepsy, neurodegeneration & cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5597608/
https://www.ncbi.nlm.nih.gov/pubmed/28904337
http://dx.doi.org/10.1038/s41598-017-10675-6
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