Iron sequestration

Iron sequestration refers **not to a specific molecule or receptor**, but rather **to a host-driven biological process in which various proteins bind and withhold free iron from circulation**, thereby limiting its availability for invading pathogens—a phenomenon known as nutritional immunity. Key molecular players in this system include transferrins (e.g., serum transferrin), lactoferrin, ferritin, calprotectin, hepcidin-regulated ferroportin degradation, and others. These molecules act collectively during infection or inflammation; their upregulation leads to hypoferremia—reduced serum/plasma levels of available (“free”) iron—which starves microbes that require it for growth while also protecting tissues from oxidative damage caused by excess unbound (“labile”) iron. This mechanism plays an important role in innate immune defense against bacterial and fungal infections. However, excessive activation—such as during chronic inflammatory states—can contribute directly to anemia ("anemia of chronic disease" or "anemia of inflammation") because sequestered stores are unavailable even for normal erythropoiesis. Because "iron sequestration" describes an integrated physiological response involving multiple molecular actors rather than any one druggable target protein/receptor/enzyme/transporter/etc., it should **not be considered a canonical therapeutic target itself**, though individual components within the pathway may be targeted pharmacologically. “Iron sequestration is a recognized innate immune mechanism against invading pathogens mediated by iron-binding proteins called transferrins.” “By binding and sequestering excess iron, ferritin prevents pathogens from accessing this essential nutrient…” “Anemia…is characterized by hypoferremia due to increased production…of hepcidin…which blocks dietary absorption…and traps recycled macrophage-derived Fe within storage sites.”

Other names

Nutritional immunity (when referring to host iron withholding)Iron withholdingHypoferremia (in the context of inflammation or infection)

Drugs that affect this process generally act by: - Chelating free iron to reduce its bioavailability for pathogens or limit toxicity. - Modulating expression/activity of proteins like hepcidin, transferrin, ferritin, lactoferrin, ferroportin.