title: Control of immunopathology during Plasmodium infection by hepcidin.
abstract: Malaria is a major health problem affecting millions of people annually especially in underdeveloped countries. Mutations causing alterations in hemoglobin production or structure are known to afford protection against the development of severe forms of malaria. Not surprinsingly, these hemoglobin disorders are present at high frequency in areas where malaria is endemic, indicating a survival advantage for individuals carrying them. Despite many years of research, the exact mechanisms underlying the protection afforded by hemoglobinopathies against severe forms of malaria have not yet found a definitive answer. One feature of hemoglobinopathies, observed both in humans and mice, is the fact that individuals carrying these disorders express low levels of the hormone hepcidin that plays a major role in iron homeostasis. Hepcidin acts by binding to the iron exporter ferroportin and inducing its degradation. When hepcidin levels are low, ferroportin expression in cells is sustained leading to export of intracellular iron. Importantly, low intracellular iron content may affect activation of innate immune cells leading to diminished production of pro-inflammatory cytokines. Notably, several lines of evidence support the notion that development of severe forms of malaria is dependent on immune-mediated damage, caused by unfettered immune responses. Herein the hypothesis that hemoglobinopathies afford protection against severe forms of malaria by limiting exacerbated immune activation, via a mechanism that involves low hepcidin expression, is discussed.
authors: Instituto Gulbenkian de Ciência, Oeiras, Portugal. address: ivomarguti@yahoo.com.br
authors: Ivo
authors: I
authors: Marguti
mesh_terms: D000818:Animals; D006453:Hemoglobinopathies / Q000378:metabolism* / Q000469:parasitology; D064451:Hepcidins / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007113:Immunity, Innate; D007501:Iron / Q000378:metabolism; D008288:Malaria / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology / Q000517:prevention & control; D051379:Mice; D010961:Plasmodium / Q000378:metabolism
chemical_list: D064451:Hepcidins; D007501:Iron