Elevated basal hepcidin levels in the liver may inhibit the development of malaria infection: another piece towards solving the malaria puzzle?

BACKGROUND: Inflammatory cytokines play a crucial role in the human immune response to infection by malaria. During the initial sporozoite infection of the liver the presence of Interleukin-6 (IL-6) can be determinant. IL-6 controls systemic iron homeostasis through hepcidin, which is produced mainly by hepatocytes. An elevated basal hepcidin level in the liver can be induced by chronic inflammatory disease. Hepcidin is also a peptide with antimicrobial properties. PRESENTATION OF THE HYPOTHESIS: We hypothesize that elevated basal hepcidin levels in the liver inhibit the development of malaria infection. When hepcidin is abundant, hepatocytes sequester iron, and this inhibits sporozoite development in liver-stage malaria infection. TESTING THE HYPOTHESIS: The validity of our hypothesis can be proven by observing sporozoite growth in hepcidin-treated hepatocytes, or in hepatocytes, stimulated with IL-6 to increase hepcidin levels before incubation with malaria sporozoites and observing the effect the hepcidin knockout function has on the infection. IMPLICATIONS OF THE HYPOTHESIS: Confirmation of our hypothesis could help to understand the complexity of the malaria infection.