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SUMMARY:Iron powers adaptive immunity - Dr Alexander (Hal) Drakesmith\; As
 sociate Professor of Immunology\, MRC Weatherhall Institute of Molecular M
 edicine\, University of Oxford
DTSTART:20190625T110000Z
DTEND:20190625T120000Z
UID:TALK124843@talks.cam.ac.uk
CONTACT:Bobbie Claxton
DESCRIPTION:Adaptive immunity requires the activation of antigen-specific 
 lymphocytes\, which rapidly divide\, differentiate and acquire effector fu
 nctions\, 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 reg
 ulatory 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 seve
 rely attenuates the magnitude of the T-and B-cell responses to protein-in-
 adjuvant\, peptide-loaded dendritic cell and viral vector immunisation pro
 tocols. Parenteral iron supplementation to mice rescues this inhibition. L
 imiting iron acquisition reduces T-cell metabolic activity and impedes pro
 gression through the cell-cycle\, blocking proliferation. Iron deficient a
 ctivated T-cells do not fully acquire effector functions and their capacit
 y to secrete cytokines is suppressed. Furthermore\, transiently low serum 
 iron during the primary immune response alters the differentiation traject
 ory 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 in
 fluenza 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 immun
 e competence on serum iron may have broad implications\, because a lack of
  iron is the most prevalent micronutrient deficiency worldwide.
LOCATION:Babraham - The Cambridge Building - Kings Hedges Room
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