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Inhibition of ex vivo erythropoiesis by secreted and haemozoin-associated Plasmodium falciparum products

Published online by Cambridge University Press:  09 May 2018

Daniela Boehm Open the ORCID record for Daniela Boehm [Opens in a new window] ,
Lydia Healy ,
Sarah Ring  and
Angus Bell Open the ORCID record for Angus Bell [Opens in a new window]
Daniela Boehm*
Affiliation:
Department of Microbiology, School of Genetics & Microbiology, Moyne Institute of Preventive Medicine, Trinity College Dublin, Dublin 2, Ireland
Lydia Healy
Affiliation:
Department of Microbiology, School of Genetics & Microbiology, Moyne Institute of Preventive Medicine, Trinity College Dublin, Dublin 2, Ireland
Sarah Ring
Affiliation:
Department of Microbiology, School of Genetics & Microbiology, Moyne Institute of Preventive Medicine, Trinity College Dublin, Dublin 2, Ireland
Angus Bell
Affiliation:
Department of Microbiology, School of Genetics & Microbiology, Moyne Institute of Preventive Medicine, Trinity College Dublin, Dublin 2, Ireland
*
Author for correspondence: Daniela Boehm, E-mail: Daniela.Boehm@dit.ie
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Abstract

It has been estimated that up to a third of global malaria deaths may be attributable to malarial anaemia, with children and pregnant women being those most severely affected. An inefficient erythropoietic response to the destruction of both infected and uninfected erythrocytes in infections with Plasmodium spp. contributes significantly to the development and persistence of such anaemia. The underlying mechanisms, which could involve both direct inhibition of erythropoiesis by parasite-derived factors and indirect inhibition as a result of modulation of the immune response, remain poorly understood. We found parasite-derived factors in conditioned medium (CM) of blood-stage Plasmodium falciparum and crude isolates of parasite haemozoin directly to inhibit erythropoiesis in an ex vivo model based on peripheral blood haematopoietic stem cells. Erythropoiesis-inhibiting activity was detected in a fraction of CM that was sensitive to heat inactivation and protease digestion. Erythropoiesis was also inhibited by crude parasite haemozoin but not by detergent-treated, heat-inactivated or protease-digested haemozoin. These results suggest that the erythropoiesis-inhibiting activity in both cases is mediated by proteins or protein-containing biomolecules and may offer new leads to the treatment of malarial anaemia.

Keywords

Erythropoiesishaemozoinmalarial anaemiaPlasmodium falciparum
Type
Research Article
Information
Parasitology , Volume 145 , Issue 14 , December 2018 , pp. 1865 - 1875
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Copyright
Copyright © Cambridge University Press 2018 

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Footnotes

*

Present address: Daniela Boehm, School of Food Science and Environmental Health, Dublin Institute of Technology, Dublin 1, Ireland.

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