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

• Published in: Nature communications Vol. 5; no. 1; p. 4446
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.07.2014; Nature Publishing Group
• Subjects: 13; 13/106; 13/31; 14/19; 692/699/1541/13; 692/699/255/1629; Adult; Anemia; Anemia, Iron-Deficiency - drug therapy; Anemia, Iron-Deficiency - parasitology; Blood; Dietary Supplements; Disease Susceptibility; Erythrocytes - parasitology; Hemoglobin; Humanities and Social Sciences; Humans; Infections; Iron; Iron - blood; Iron - pharmacology; Malaria; Malaria, Falciparum - prevention & control; Medical research; Middle Aged; multidisciplinary; Parasites; Plasmodium falciparum - drug effects; Plasmodium falciparum - growth & development; Plasmodium falciparum - pathogenicity; Science; Science (multidisciplinary); Young Adult; North Carolina; United States > US
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms5446

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. It remains unclear why iron deficiency can protect from malaria infection. Here the authors show that iron-deficient microcytic erythrocytes are less efficiently infected by Plasmodium falciparum parasites and that iron supplementation increases the proportion of young erythrocytes more susceptible to infection.