Host iron status and iron supplementation mediate susceptibility to erythrocytic stage Plasmodium falciparum

Clark, Martha A.; Goheen, Morgan M.; Fulford, Anthony; Prentice, Andrew M.; Elnagheeb, Marwa A.; Patel, Jaymin; Fisher, Nancy; Taylor, Steve M.; Kasthuri, Raj S.; Cerami, Carla

doi:10.1038/ncomms5446

Cited by 135Malaria Research and ControlIron Metabolism and DisordersHemoglobinopathies and Related Disorders

Host iron status and iron supplementation mediate susceptibility to erythrocytic stage Plasmodium falciparum

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Clark, Martha A., Goheen, Morgan M., Fulford, Anthony, Prentice, Andrew M., Elnagheeb, Marwa A., Patel, Jaymin, Fisher, Nancy, Taylor, Steve M. +2 more·2014·Nature Communications

DOI 10.1038/ncomms5446PMC PMC4249681

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Abstract

Iron deficiency and malaria have similar global distributions, and frequently co-exist in pregnant women and young children. Where both conditions are prevalent, iron supplementation is complicated by observations that iron deficiency anaemia protects against falciparum malaria, and that iron supplements increase susceptibility to clinically significant malaria, but the mechanisms remain obscure. Here, using an in vitro parasite culture system with erythrocytes from iron-deficient and replete human donors, we demonstrate that Plasmodium falciparum infects iron-deficient erythrocytes less efficiently. In addition, owing to merozoite preference for young erythrocytes, iron supplementation of iron-deficient individuals reverses the protective effects of iron deficiency. Our results provide experimental validation of field observations reporting protective effects of iron deficiency and harmful effects of iron administration on human malaria susceptibility. Because recovery from anaemia requires transient reticulocytosis, our findings imply that in malarious regions iron supplementation should be accompanied by effective measures to prevent falciparum malaria.

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In ex vivo erythrocytes from iron-deficient donors, P. falciparum invades fewer cells and grows more slowly intracellularly than in erythrocytes from iron-replete donors.
“In ex vivo erythrocytes from iron-deficient donors, the malarial parasite Plasmodium falciparum invades fewer cells and shows slower intracellular growth than in erythrocytes from iron-replete donors66.”
From Iron homeostasis in host defence and inflammation (2015) · cites this paper as [66]

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Iron Deficiency and Iron Supplementation Conspire to Mediate Susceptibility to Erythrocytic Stage Plasmodium falciparum Infection
Clark, M. A. (2019) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/6m5p-z003
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Impact of host iron on pathogenesis of falciparum malaria: a translational field study from The Gambia
Cerami, C., Goheen, M. M., Gardner, D., Darboe, B., Danso, E., Bah, M., Bah, A., Wegmüller, R., & Prentice, A. M. (2016) · The FASEB Journal · doi:10.1096/fasebj.30.1_supplement.668.6
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Authors: Clark, M. A., Goheen, M. M., Fulford, A., Prentice, A. M., Elnagheeb, M. A., Patel, J., Fisher, N., Taylor, S. M., Kasthuri, R. S., & Cerami, C.
Affiliations: University of North Carolina at Chapel Hill (US)
London School of Hygiene & Tropical Medicine (GB)
Duke University (US)
Corresponding author: Cerami, Carla
ORCID: Goheen, Morgan M.
Prentice, Andrew M.
Elnagheeb, Marwa A.
Patel, Jaymin
Taylor, Steve M.
Kasthuri, Raj S.
Venue: Nature Communications
Publisher: Springer Science and Business Media LLC
Published: 2014-07-25
Volume: 5
Issue: 1
Pages: 4446-4446
ISSN: 2041-1723 (ISSN-L)
DOI: 10.1038/ncomms5446
PMC: PMC4249681
OpenAlex: W2124344400
Cited by: 134
References: 42
Citations by year: 2026: 9 · 2025: 8 · 2024: 10 · 2023: 12 · 2022: 8 · 2021: 8 · 2020: 8 · 2019: 13 · 2018: 13 · 2017: 15 · 2016: 19 · 2015: 11
FWCI: 14.93
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Nature Communications (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
RePEc: Research Papers in Economics (submittedVersion)
UNC Libraries
Funders: National Cancer Institute (P30-CA06086, P30CA016086)
National Institute of Allergy and Infectious Diseases (K08AI100924)
National Institute of Child Health and Human Development
Eunice Kennedy Shriver National Institute of Child Health and Human Development (U01HD061235)
Topics: Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
Keywords: Plasmodium falciparum, iron deficiency, iron supplementation, malaria susceptibility, erythrocyte infection, reticulocytosis, anemia, pregnancy, young children, host-parasite interactions
MeSH terms: Adult, Disease Susceptibility, Erythrocytes, Humans, Iron, Middle Aged, Plasmodium falciparum, Malaria, Falciparum, Anemia, Iron-Deficiency, Dietary Supplements, Young Adult

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Host iron status and iron supplementation mediate susceptibility to erythrocytic stage Plasmodium falciparum

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