Distinct mechanisms of inadequate erythropoiesis induced by tumor necrosis factor alpha or malarial pigment

PloS One
Abigail A LamikanraDavid J Roberts

Abstract

The role of infection in erythropoietic dysfunction is poorly understood. In children with P. falciparum malaria, the by-product of hemoglobin digestion in infected red cells (hemozoin) is associated with the severity of anemia which is independent of circulating levels of the inflammatory cytokine tumor necrosis alpha (TNF-α). To gain insight into the common and specific effects of TNF-α and hemozoin on erythropoiesis, we studied the gene expression profile of purified primary erythroid cultures exposed to either TNF-α (10 ng/ml) or to hemozoin (12.5 μg/ml heme units) for 24 hours. Perturbed gene function was assessed using co-annotation of associated gene ontologies and expression of selected genes representative of the profile observed was confirmed by real time PCR (rtPCR). The changes in gene expression induced by each agent were largely distinct; many of the genes significantly modulated by TNF-α were not affected by hemozoin. The genes modulated by TNF-α were significantly enriched for those encoding proteins involved in the control of type 1 interferon signalling and the immune response to viral infection. In contrast, genes induced by hemozoin were significantly enriched for functional roles in regulation of transcript...Continue Reading

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Citations

Dec 15, 2015·FEMS Microbiology Reviews·Katrien DeroostPhilippe E Van den Steen
Apr 9, 2016·Medicine·Cho NaingVictor Nyunt Wai
Dec 27, 2016·Frontiers in Cellular and Infection Microbiology·Paulo R R TotinoMaria de Fátima Ferreira-da-Cruz
Oct 21, 2018·Malaria Journal·Nicholas J White

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Datasets Mentioned

BETA
GSE65577

Methods Mentioned

BETA
flow cytometry
ubiquitination
fluorescence activated sorter
PCR
Assay

Software Mentioned

Bioconductor
Genesis
GeneCodis
R
GeneChip Operating Software ( GCOS
Weasel
Excel
WinMDI

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