Hepcidin-Mediated Hypoferremia Disrupts Immune Responses to Vaccination and Infection

Background: How specific nutrients influence adaptive immunity is of broad interest Iron deficiency is the most common micronutrient deficiency worldwide and imparts a significant burden of global disease: however, is effects on immunity remain unclear Methods: We used a hepcidin mimetic and several genetic models to examine the effect of low iron avaliability on T cells in vitro and on immune responses to vaccines and viral infection in mice. We examined humeral immunity in human patients with raised hepcidin and low serum iron caused by mutant TMPRSS6 We tested the effect of iron supplementation on vaccination-induced humoral immunity in piglets, a natural model of iron deficiency. Findings: We show that low serum iron (hypoferremia), caused by ncreased hepcidin severely impairs effector and memory responses to mmunizations. The intensified metabolism at activated lymphocytes requires the support of enhanced iron acquisition, which is facilitated by IRP1/2 and TFRC. Accordingly providing extra iron improved the response to vaccination in hypoferremic mice and piglets, whIle conversely, hypoferremic humans with chronically increased hepcidin have reduced concentrations of antibodies specific for certain pathogens. Imposing hypoferremia blunted the T cell, B cell, and neutralizing antibody responses to influenza virus infection in mice, allowing the virus to persist and exacerbating lung inflammation and morbidity. Conclusions: Hypoterremia, a well-conserved physiological innate response to infection, can counteract the development of adaptive immunity. This nutrient trade-off is relevant for understanding and improving Immune responses to infections and vaccines in the globally common contexts of iron deficiency and inflammatory disorders.

Automated summary

The study found that hypoferremia severely impairs immune responses to vaccinations, but providing extra iron can improve this situation. Experiments on mice and piglets revealed that iron deficiency weakens immunity to vaccines and pathogens.