Does HFE Genotype Impact Macrophage Phenotype in Disease Process and Therapeutic Response?

Iron is a critical cofactor involved in many important physiological processes throughout the human body. Therefore, mismanagement of iron can lead to numerous unfavorable effects, such as the generation of toxic reactive oxygen species during iron overload. Iron mismanagement is also a key component of multiple neurodegenerative diseases and cancer. One way in which iron overload occurs is through a mutation within the HFE, high iron, gene. However, the mechanism by which HFE effects these diseases has yet to be elucidated. In this review, we consider how the HFE genotype may influence the role of macrophages and microglia (the resident macrophage of the brain) in neurodegenerative disease and cancer. Macrophages appear to redistribute their iron to parenchymal cells when an HFE mutation is present, resulting in increased vulnerability to neurodegenerative diseases and cancer through macrophage mishandling of iron.