Iron powers adaptive immunityAdaptive immunity requires the activation of antigen-specific lymphocytes, which rapidly divide, differentiate and acquire effector functions, and eventually generate immunological memory. Several metabolic pathways are co-opted during this process to provide energy and nutrients, but even though iron underpins much of cellular biochemistry, the role of iron in immunity has remained unclear. By using hepcidin, the iron regulatory hormone, to rapidly and transiently decrease serum iron, we show that systemic iron homeostasis is critical for antigen-specific immunity. Hepcidin decreases the amount of iron available to lymphocytes, and severely attenuates the magnitude of the T-and B-cell responses to protein-in-adjuvant, peptide-loaded dendritic cell and viral vector immunisation protocols. Parenteral iron supplementation to mice rescues this inhibition. Limiting iron acquisition reduces T-cell metabolic activity and impedes progression through the cell-cycle, blocking proliferation. Iron deficient activated T-cells do not fully acquire effector functions and their capacity to secrete cytokines is suppressed. Furthermore, transiently low serum iron during the primary immune response alters the differentiation trajectory of T-cells such that subsequent memory and secondary recall responses remain suboptimal several weeks after serum iron has normalised. Low serum iron also decreases the primary T- and B-cell response to experimental influenza virus infection such that neutralising antibodies are undetectable, and clearance of viral mRNA from the lung and the symptomatic recovery of infected animals are also impaired. The evidence of dependence of immune competence on serum iron may have broad implications, because a lack of iron is the most prevalent micronutrient deficiency worldwide.
If you would like to attend this seminar, please contact us to arrange site access.
|Starts||12:00 pm - 25/06/2019|
|Ends||01:00 pm - 25/06/2019|
|Location||The Cambridge Building - Kings Hedges Room|
|Speaker||Dr Alexander Drakesmith|
|Speaker Affiliation||Associate Professor of Immunology, MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford|
18 June, 2019