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Integrative analysis associates monocytes with insufficient erythropoiesis during acute Plasmodium cynomolgi malaria in rhesus macaques
BACKGROUND: Mild to severe anaemia is a common complication of malaria that is caused in part by insufficient erythropoiesis in the bone marrow. This study used systems biology to evaluate the transcriptional and alterations in cell populations in the bone marrow during Plasmodium cynomolgi infectio...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5610412/ https://www.ncbi.nlm.nih.gov/pubmed/28938907 http://dx.doi.org/10.1186/s12936-017-2029-z |
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author | Tang, Yan Joyner, Chester J. Cabrera-Mora, Monica Saney, Celia L. Lapp, Stacey A. Nural, Mustafa V. Pakala, Suman B. DeBarry, Jeremy D. Soderberg, Stephanie Kissinger, Jessica C. Lamb, Tracey J. Galinski, Mary R. Styczynski, Mark P. |
author_facet | Tang, Yan Joyner, Chester J. Cabrera-Mora, Monica Saney, Celia L. Lapp, Stacey A. Nural, Mustafa V. Pakala, Suman B. DeBarry, Jeremy D. Soderberg, Stephanie Kissinger, Jessica C. Lamb, Tracey J. Galinski, Mary R. Styczynski, Mark P. |
author_sort | Tang, Yan |
collection | PubMed |
description | BACKGROUND: Mild to severe anaemia is a common complication of malaria that is caused in part by insufficient erythropoiesis in the bone marrow. This study used systems biology to evaluate the transcriptional and alterations in cell populations in the bone marrow during Plasmodium cynomolgi infection of rhesus macaques (a model of Plasmodium vivax malaria) that may affect erythropoiesis. RESULTS: An appropriate erythropoietic response did not occur to compensate for anaemia during acute cynomolgi malaria despite an increase in erythropoietin levels. During this period, there were significant perturbations in the bone marrow transcriptome. In contrast, relapses did not induce anaemia and minimal changes in the bone marrow transcriptome were detected. The differentially expressed genes during acute infection were primarily related to ongoing inflammatory responses with significant contributions from Type I and Type II Interferon transcriptional signatures. These were associated with increased frequency of intermediate and non-classical monocytes. Recruitment and/or expansion of these populations was correlated with a decrease in the erythroid progenitor population during acute infection, suggesting that monocyte-associated inflammation may have contributed to anaemia. The decrease in erythroid progenitors was associated with downregulation of genes regulated by GATA1 and GATA2, two master regulators of erythropoiesis, providing a potential molecular basis for these findings. CONCLUSIONS: These data suggest the possibility that malarial anaemia may be driven by monocyte-associated disruption of GATA1/GATA2 function in erythroid progenitors resulting in insufficient erythropoiesis during acute infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12936-017-2029-z) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5610412 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-56104122017-10-10 Integrative analysis associates monocytes with insufficient erythropoiesis during acute Plasmodium cynomolgi malaria in rhesus macaques Tang, Yan Joyner, Chester J. Cabrera-Mora, Monica Saney, Celia L. Lapp, Stacey A. Nural, Mustafa V. Pakala, Suman B. DeBarry, Jeremy D. Soderberg, Stephanie Kissinger, Jessica C. Lamb, Tracey J. Galinski, Mary R. Styczynski, Mark P. Malar J Research BACKGROUND: Mild to severe anaemia is a common complication of malaria that is caused in part by insufficient erythropoiesis in the bone marrow. This study used systems biology to evaluate the transcriptional and alterations in cell populations in the bone marrow during Plasmodium cynomolgi infection of rhesus macaques (a model of Plasmodium vivax malaria) that may affect erythropoiesis. RESULTS: An appropriate erythropoietic response did not occur to compensate for anaemia during acute cynomolgi malaria despite an increase in erythropoietin levels. During this period, there were significant perturbations in the bone marrow transcriptome. In contrast, relapses did not induce anaemia and minimal changes in the bone marrow transcriptome were detected. The differentially expressed genes during acute infection were primarily related to ongoing inflammatory responses with significant contributions from Type I and Type II Interferon transcriptional signatures. These were associated with increased frequency of intermediate and non-classical monocytes. Recruitment and/or expansion of these populations was correlated with a decrease in the erythroid progenitor population during acute infection, suggesting that monocyte-associated inflammation may have contributed to anaemia. The decrease in erythroid progenitors was associated with downregulation of genes regulated by GATA1 and GATA2, two master regulators of erythropoiesis, providing a potential molecular basis for these findings. CONCLUSIONS: These data suggest the possibility that malarial anaemia may be driven by monocyte-associated disruption of GATA1/GATA2 function in erythroid progenitors resulting in insufficient erythropoiesis during acute infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12936-017-2029-z) contains supplementary material, which is available to authorized users. BioMed Central 2017-09-22 /pmc/articles/PMC5610412/ /pubmed/28938907 http://dx.doi.org/10.1186/s12936-017-2029-z 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 Tang, Yan Joyner, Chester J. Cabrera-Mora, Monica Saney, Celia L. Lapp, Stacey A. Nural, Mustafa V. Pakala, Suman B. DeBarry, Jeremy D. Soderberg, Stephanie Kissinger, Jessica C. Lamb, Tracey J. Galinski, Mary R. Styczynski, Mark P. Integrative analysis associates monocytes with insufficient erythropoiesis during acute Plasmodium cynomolgi malaria in rhesus macaques |
title | Integrative analysis associates monocytes with insufficient erythropoiesis during acute Plasmodium cynomolgi malaria in rhesus macaques |
title_full | Integrative analysis associates monocytes with insufficient erythropoiesis during acute Plasmodium cynomolgi malaria in rhesus macaques |
title_fullStr | Integrative analysis associates monocytes with insufficient erythropoiesis during acute Plasmodium cynomolgi malaria in rhesus macaques |
title_full_unstemmed | Integrative analysis associates monocytes with insufficient erythropoiesis during acute Plasmodium cynomolgi malaria in rhesus macaques |
title_short | Integrative analysis associates monocytes with insufficient erythropoiesis during acute Plasmodium cynomolgi malaria in rhesus macaques |
title_sort | integrative analysis associates monocytes with insufficient erythropoiesis during acute plasmodium cynomolgi malaria in rhesus macaques |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5610412/ https://www.ncbi.nlm.nih.gov/pubmed/28938907 http://dx.doi.org/10.1186/s12936-017-2029-z |
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