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Haematologica. 2017 Jan;102(1):60-68. doi: 10.3324/haematol.2016.150227. Epub 2016 Sep 22.

Erythroferrone contributes to hepcidin repression in a mouse model of malarial anemia.

Author information

1
IRSD, Université de Toulouse, INSERM U1220, INRA U1416, ENVT, UPS, Toulouse, France.
2
CPTP, Université de Toulouse, CNRS U5282, Inserm U1043, UPS, Toulouse, France.
3
Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles, USA.
4
Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, USA.
5
IRSD, Université de Toulouse, INSERM U1220, INRA U1416, ENVT, UPS, Toulouse, France leon.kautz@inserm.fr helene.coppin@inserm.fr.

Abstract

Malaria, a major global health challenge worldwide, is accompanied by a severe anemia secondary to hemolysis and increased erythrophagocytosis. Iron is an essential functional component of erythrocyte hemoglobin and its availability is controlled by the liver-derived hormone hepcidin. We examined the regulation of hepcidin during malarial infection in mice using the rodent parasite Plasmodium berghei K173. Mice infected with Plasmodium berghei K173 develop a severe anemia and die after 18 to 22 days without cerebral malaria. During the early phase of blood-stage infection (days 1 to 5), a strong inflammatory signature was associated with an increased production of hepcidin. Between days 7 and 18, while infection progressed, red blood cell count, hemoglobin and hematocrit dramatically decreased. In the late phase of malarial infection, hepcidin production was reduced concomitantly to an increase in the messenger RNA expression of the hepcidin suppressor erythroferrone in the bone marrow and the spleen. Compared with wild-type mice, Erfe-/- mice failed to adequately suppress hepcidin expression after infection with Plasmodium berghei K173. Importantly, the sustained production of hepcidin allowed by erythroferrone ablation was associated with decreased parasitemia, providing further evidence that transient iron restriction could be beneficial in the treatment of malaria.

PMID:
27658439
PMCID:
PMC5210233
DOI:
10.3324/haematol.2016.150227
[Indexed for MEDLINE]
Free PMC Article

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