RESUMEN
Iron recycling prevents the development of anemia under homeostatic conditions. Whether iron recycling was co-opted as a defense strategy to prevent the development of anemia in response to infection is unclear. We find that in severe Plasmodium falciparum malaria, the onset of life-threatening anemia is associated with acute kidney injury (AKI), irrespective of parasite load. Using a well-established experimental rodent model of malaria anemia, we identify a transcriptional response that endows renal proximal tubule epithelial cells (RPTECs) with the capacity to store and recycle iron during P. chabaudi chabaudi (Pcc) infection. This response encompasses the induction of ferroportin 1/SLC40A1, which exports iron from RPTECs and counteracts AKI while supporting compensatory erythropoiesis and preventing the onset of life-threatening malarial anemia. Iron recycling by myeloid cells is dispensable to this protective response, suggesting that RPTECs provide an iron-recycling salvage pathway that prevents the pathogenesis of life-threatening malarial anemia.
Asunto(s)
Lesión Renal Aguda , Anemia , Malaria Falciparum , Malaria , Humanos , Anemia/etiología , Malaria/complicaciones , Malaria/parasitología , Eritropoyesis/fisiología , Malaria Falciparum/complicaciones , HierroRESUMEN
Hereditary hemochromatosis (HH) is one of the most common genetically transmitted conditions in individuals of Northern European ancestry. The disease is characterized by excessive intestinal absorption of dietary iron, resulting in pathologically high iron storage in tissues and organs. If left untreated, HH can damage joints and organs, and eventually lead to death. There are four main classes of HH, as well as five individual molecular subtypes, caused by mutations in five genes, and the approaches implemented in the discovery of each HH type have specific histories and unique aspects. In this chapter, we review the genetics of the different HH types, including the strategies used to detect the causal variants in each case and the manner in which genetic variants were found to affect iron metabolism.