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. Author manuscript; available in PMC: 2014 Oct 17.
Published in final edited form as: Nat Med. 2011 May 15;17(6):732–737. doi: 10.1038/nm.2368

Figure 3. Hepcidin increase induction during blood stageblood-stage infection leads to iron redistribution and restricts Plasmodium liver infection.

Figure 3

Plasmodium load and relative hamp1 expression measurements after sporozoite infection of naïve mice (Control) or mice previously infected with P. berghei NK65 (PbNK). (a) Liver load (red), relative hamp1 expression (black) and peripheral blood parasitaemia (x-axis), 40h after PbA-GFP sporozoite injection of mice infected 3 days before with 103–7 PbNK iRBCs. (b) 40h after PbA-GFP sporozoite infection of mice infected 5 days before with 106 PbNK iRBCs, with or without 2 days chloroquine treatment (CQ). (c) EEF and ferritin distribution in livers as in (b) (bar = 10μm.). (d) Total non-heme iron quantification of spleen (left axis) and liver hepatocytes (right axis) as in (b). (e) Hamp1 expression of mouse primary hepatocytes 24h post-treatment with serum from non-infected mice (NI serum) or PbNK infected mice (PbNK serum), in the presence of dorsomorphin or IL-6 depleting antibody (aIL-6). (f) 36h after PbA-GFP sporozoite infection of Huh7 hepatoma cells in the presence of bathophenanthrolinedisulfonate (BPS). Plot shows one representative dataset of triplicate samples. (g–h) Effect of Desferrioxamine (DFO) and Ferric Ammonium Citrate (FAC) on Plasmodium infection in Huh7 hepatoma cells and liver infection. Representative images (g), EEF area quantification (h, left axis) 36h after PbA-GFP sporozoite infection or Plasmodium liver load (h, right axis) 40h after PbA-GFP sporozoite injection of pre-treated mice. (bar = 10μm.) Results are expressed as the mean ± s.d. of 3 independent infections. (i) 40h post PbA sporozoite injection of mice treated with human hepcidin peptide (Peptide); of mice expressing a human hamp transgene (Transgenic); and of mice infected with hamp expressing adenovirus. (j) Schematic representation of hepcidin-mediated iron redistribution and regulation of superinfection in malaria. (*P <0.05; **P <0.01, Ttest). Results expressed as mean±s.d. of 3 independent infections (n≥5 mice per group).