title: Hepcidin is regulated during blood-stage malaria and plays a protective role in malaria infection.
abstract: Hepcidin is one of the regulators of iron metabolism. The expression of hepcidin is induced in spleens and livers of mice infected with pathogenic bacteria. Recent studies have indicated that serum hepcidin level is also increased in human subjects infected with Plasmodium falciparum. The mechanism of the regulation of hepcidin expression and its role in the infection of malaria remains unknown. In this study, we determined the expression of hepcidin in livers of mice infected with Plasmodium berghei. The expression of hepcidin in the liver was upregulated and downregulated during the early and late stages of malaria infection, respectively. Inflammation and erythropoietin, rather than the iron-sensing pathway, are involved in the regulation of hepcidin expression in livers of infected mice. Meanwhile, we investigated the effect of hepcidin on the survival of mice infected with P. berghei. Treatment of malaria-infected mice with anti-hepcidin neutralizing Abs promoted the rates of parasitemia and mortality. In contrast, lentiviral vector-mediated overexpression of hepcidin improved the outcome of P. berghei infection in mice. Our data demonstrate an important role of hepcidin in modulating the course and outcome of blood-stage malaria.
authors.affiliation: Laboratory for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming, Yunnan 650091, China.
authors.forename: Hai-Zhen
authors.initials: HZ
authors.lastname: Wang
authors.forename: Ying-Xin
authors.initials: YX
authors.lastname: He
authors.forename: Chun-Ju
authors.initials: CJ
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Cheng-Gang
authors.initials: CG
authors.lastname: Zou
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000097:blood* / Q000627:therapeutic use; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D016207:Cytokines / Q000097:blood / Q000502:physiology; D006420:Hemeproteins / Q000008:administration & dosage; D064451:Hepcidins; D018836:Inflammation Mediators / Q000097:blood / Q000502:physiology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood; D008109:Liver Diseases, Parasitic / Q000097:blood / Q000276:immunology / Q000517:prevention & control; D016779:Malaria, Cerebral / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008813:Mice, Inbred ICR; D010962:Plasmodium berghei / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology
chemical_list: D000962:Antimalarials; D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; C578702:HAMP protein, human; C579599:Hamp protein, mouse; D006420:Hemeproteins; D064451:Hepcidins; D018836:Inflammation Mediators; D015850:Interleukin-6; C020753:hemozoin