Integrative analysis associates monocytes with insufficient erythropoiesis during acute Plasmodium cynomolgi malaria in rhesus macaques
Abstract 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...
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ftdoajarticles:oai:doaj.org/article:ebd3d91dc30544f787f3ee9fc2b67da0 2023-05-15T15:11:17+02:00 Integrative analysis associates monocytes with insufficient erythropoiesis during acute Plasmodium cynomolgi malaria in rhesus macaques Yan Tang Chester J. Joyner Monica Cabrera-Mora Celia L. Saney Stacey A. Lapp Mustafa V. Nural Suman B. Pakala Jeremy D. DeBarry Stephanie Soderberg the MaHPIC Consortium Jessica C. Kissinger Tracey J. Lamb Mary R. Galinski Mark P. Styczynski 2017-09-01T00:00:00Z https://doi.org/10.1186/s12936-017-2029-z https://doaj.org/article/ebd3d91dc30544f787f3ee9fc2b67da0 EN eng BMC http://link.springer.com/article/10.1186/s12936-017-2029-z https://doaj.org/toc/1475-2875 doi:10.1186/s12936-017-2029-z 1475-2875 https://doaj.org/article/ebd3d91dc30544f787f3ee9fc2b67da0 Malaria Journal, Vol 16, Iss 1, Pp 1-16 (2017) Plasmodium cynomolgi GATA1 Nonhuman primates Relapse Plasmodium vivax Bone marrow Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2017 ftdoajarticles https://doi.org/10.1186/s12936-017-2029-z 2022-12-31T03:02:18Z Abstract 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 16 1 |
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Directory of Open Access Journals: DOAJ Articles |
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Plasmodium cynomolgi GATA1 Nonhuman primates Relapse Plasmodium vivax Bone marrow Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
Plasmodium cynomolgi GATA1 Nonhuman primates Relapse Plasmodium vivax Bone marrow Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Yan Tang Chester J. Joyner Monica Cabrera-Mora Celia L. Saney Stacey A. Lapp Mustafa V. Nural Suman B. Pakala Jeremy D. DeBarry Stephanie Soderberg the MaHPIC Consortium Jessica C. Kissinger Tracey J. Lamb Mary R. Galinski Mark P. Styczynski Integrative analysis associates monocytes with insufficient erythropoiesis during acute Plasmodium cynomolgi malaria in rhesus macaques |
topic_facet |
Plasmodium cynomolgi GATA1 Nonhuman primates Relapse Plasmodium vivax Bone marrow Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract 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. |
format |
Article in Journal/Newspaper |
author |
Yan Tang Chester J. Joyner Monica Cabrera-Mora Celia L. Saney Stacey A. Lapp Mustafa V. Nural Suman B. Pakala Jeremy D. DeBarry Stephanie Soderberg the MaHPIC Consortium Jessica C. Kissinger Tracey J. Lamb Mary R. Galinski Mark P. Styczynski |
author_facet |
Yan Tang Chester J. Joyner Monica Cabrera-Mora Celia L. Saney Stacey A. Lapp Mustafa V. Nural Suman B. Pakala Jeremy D. DeBarry Stephanie Soderberg the MaHPIC Consortium Jessica C. Kissinger Tracey J. Lamb Mary R. Galinski Mark P. Styczynski |
author_sort |
Yan Tang |
title |
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_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_sort |
integrative analysis associates monocytes with insufficient erythropoiesis during acute plasmodium cynomolgi malaria in rhesus macaques |
publisher |
BMC |
publishDate |
2017 |
url |
https://doi.org/10.1186/s12936-017-2029-z https://doaj.org/article/ebd3d91dc30544f787f3ee9fc2b67da0 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 16, Iss 1, Pp 1-16 (2017) |
op_relation |
http://link.springer.com/article/10.1186/s12936-017-2029-z https://doaj.org/toc/1475-2875 doi:10.1186/s12936-017-2029-z 1475-2875 https://doaj.org/article/ebd3d91dc30544f787f3ee9fc2b67da0 |
op_doi |
https://doi.org/10.1186/s12936-017-2029-z |
container_title |
Malaria Journal |
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16 |
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1 |
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1766342165256994816 |