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Erythrocytic iron deficiency enhances susceptibility to Plasmodium chabaudi infection in mice carrying a missense mutation in transferrin receptor 1

Lelliott, Patrick; McMorran, Brendan; Foote, Simon; Burgio, Gaetan

Description

The treatment of iron deficiency in areas of high malaria transmission is complicated by evidence which suggests that iron deficiency anemia protects against malaria, while iron supplementation increases malaria risk. Iron deficiency anemia results in an array of pathologies, including reduced systemic iron bioavailability and abnormal erythrocyte physiology; however, the mechanisms by which these pathologies influence malaria infection are not well defined. In the present study, the response...[Show more]

dc.contributor.authorLelliott, Patrick
dc.contributor.authorMcMorran, Brendan
dc.contributor.authorFoote, Simon
dc.contributor.authorBurgio, Gaetan
dc.date.accessioned2016-02-24T22:41:25Z
dc.identifier.issn0019-9567
dc.identifier.urihttp://hdl.handle.net/1885/98681
dc.description.abstractThe treatment of iron deficiency in areas of high malaria transmission is complicated by evidence which suggests that iron deficiency anemia protects against malaria, while iron supplementation increases malaria risk. Iron deficiency anemia results in an array of pathologies, including reduced systemic iron bioavailability and abnormal erythrocyte physiology; however, the mechanisms by which these pathologies influence malaria infection are not well defined. In the present study, the response to malaria infection was examined in a mutant mouse line, TfrcMRI24910, identified during an N-ethyl-N-nitrosourea (ENU) screen. This line carries a missense mutation in the gene for transferrin receptor 1 (TFR1). Heterozygous mice exhibited reduced erythrocyte volume and density, a phenotype consistent with dietary iron deficiency anemia. However, unlike the case in dietary deficiency, the erythrocyte half-life, mean corpuscular hemoglobin concentration, and intraerythrocytic ferritin content were unchanged. Systemic iron bioavailability was also unchanged, indicating that this mutation results in erythrocytic iron deficiency without significantly altering overall iron homeostasis. When infected with the rodent malaria parasite Plasmodium chabaudi adami, mice displayed increased parasitemia and succumbed to infection more quickly than their wild-type littermates. Transfusion of fluorescently labeled erythrocytes into malaria parasite-infected mice demonstrated an erythrocyte-autonomous enhanced survival of parasites within mutant erythrocytes. Together, these results indicate that TFR1 deficiency alters erythrocyte physiology in a way that is similar to dietary iron deficiency anemia, albeit to a lesser degree, and that this promotes intraerythrocytic parasite survival and an increased susceptibility to malaria in mice. These findings may have implications for the management of iron deficiency in the context of malaria.
dc.publisherAmerican Society for Microbiology
dc.rightsAuthor/s retain copyright
dc.sourceInfection and Immunity
dc.titleErythrocytic iron deficiency enhances susceptibility to Plasmodium chabaudi infection in mice carrying a missense mutation in transferrin receptor 1
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume83
dc.date.issued2015
local.identifier.absfor060499 - Genetics not elsewhere classified
local.identifier.absfor110803 - Medical Parasitology
local.identifier.absfor111203 - Cancer Genetics
local.identifier.ariespublicationU3488905xPUB6772
local.type.statusPublished Version
local.contributor.affiliationLelliott, Patrick, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationMcMorran, Brendan, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationFoote, Simon, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationBurgio, Gaetan, College of Medicine, Biology and Environment, ANU
local.bibliographicCitation.issue11
local.bibliographicCitation.startpage4322
local.bibliographicCitation.lastpage4334
local.identifier.doi10.1128/IAI.00926-15
dc.date.updated2016-02-24T10:11:51Z
local.identifier.scopusID2-s2.0-84947560011
dcterms.accessRightsOpen Access
CollectionsANU Research Publications

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