Openly accessible

Acute Plasmodium berghei Mouse Infection Elicits Perturbed Erythropoiesis With Features That Overlap With Anemia of Chronic Disease

Lakkavaram, Asha, Lundie, Rachel J., Do, Hang, Ward, Alister C. and De Koning-Ward, Tania F. 2020, Acute Plasmodium berghei Mouse Infection Elicits Perturbed Erythropoiesis With Features That Overlap With Anemia of Chronic Disease, Frontiers in Microbiology, vol. 11, pp. 1-19, doi: 10.3389/fmicb.2020.00702.

Attached Files
Name Description MIMEType Size Downloads
lakkavaram-acuteplasmodium-2020.pdf Published version application/pdf 5.13MB 6

Title Acute Plasmodium berghei Mouse Infection Elicits Perturbed Erythropoiesis With Features That Overlap With Anemia of Chronic Disease
Author(s) Lakkavaram, Asha
Lundie, Rachel J.
Do, Hang
Ward, Alister C.ORCID iD for Ward, Alister C. orcid.org/0000-0001-7945-7975
De Koning-Ward, Tania F.ORCID iD for De Koning-Ward, Tania F. orcid.org/0000-0001-5810-8063
Journal name Frontiers in Microbiology
Volume number 11
Article ID 702
Start page 1
End page 19
Total pages 19
Publisher Frontiers Media
Place of publication Lausanne, Switzerland
Publication date 2020-04-16
ISSN 1664-302X
Keyword(s) Plasmodium
anemia
erythropoiesis
hematopoiesis
STAT5
Science & Technology
Life Sciences & Biomedicine
Microbiology
SEVERE MALARIAL ANEMIA
NECROSIS-FACTOR-ALPHA
MIGRATION-INHIBITORY FACTOR
ERYTHROID PROGENITOR CELLS
HEMATOPOIETIC STEM-CELLS
BONE-MARROW
FALCIPARUM MALARIA
SERUM-LEVELS
INEFFECTIVE ERYTHROPOIESIS
IFN-GAMMA
Summary Severe malaria anemia is one of the most common causes of morbidity and mortality arising from infection with Plasmodium falciparum. The pathogenesis of malarial anemia is complex, involving both parasite and host factors. As mouse models of malaria also develop anemia, they can provide a useful resource to study the impact of Plasmodium infections and the resulting host innate immune response on erythropoiesis. In this study, we have characterized the bone marrow and splenic responses of the erythroid as well as other hematopoietic lineages after an acute infection of Balb/c mice with Plasmodium berghei. Such characterization of the hematopoietic changes is critical to underpin future studies, using knockout mice and transgenic parasites, to tease out the interplay between host genes and parasite modulators implicated in susceptibility to malaria anemia. P. berghei infection led to a clear perturbation of steady-state erythropoiesis, with the most profound defects in polychromatic and orthochromatic erythroblasts as well as erythroid colony- and burst-forming units (CFU-E and BFU-E), resulting in an inability to compensate for anemia. The perturbation in erythropoiesis was not attributable to parasites infecting erythroblasts and affecting differentiation, nor to insufficient erythropoietin (EPO) production or impaired activation of the Signal transducer and activator of transcription 5 (STAT5) downstream of the EPO receptor, indicating EPO-signaling remained functional in anemia. Instead, the results point to acute anemia in P. berghei-infected mice arising from increased myeloid cell production in order to clear the infection, and the concomitant release of pro-inflammatory cytokines and chemokines from myeloid cells that inhibit erythroid development, in a manner that resembles the pathophysiology of anemia of chronic disease.
Language eng
DOI 10.3389/fmicb.2020.00702
Indigenous content off
Field of Research 0502 Environmental Science and Management
0503 Soil Sciences
0605 Microbiology
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2020, Lakkavaram, Lundie, Do, Ward and de Koning-Ward
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30136558

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
Open Access Collection
Connect to link resolver
 
Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved.

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.

Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 0 times in TR Web of Science
Scopus Citation Count Cited 0 times in Scopus
Google Scholar Search Google Scholar
Access Statistics: 12 Abstract Views, 6 File Downloads  -  Detailed Statistics
Created: Thu, 07 May 2020, 20:45:22 EST

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.