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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
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.
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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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