Hepcidin-Mediated Hypoferremia Disrupts Immune Responses to Vaccination and Infection.
T-cells
adaptive immunity
global health
hepcidin
hypoferremia
immunometabolism
infection
influenza virus
iron
vaccination
Journal
Med (New York, N.Y.)
ISSN: 2666-6340
Titre abrégé: Med
Pays: United States
ID NLM: 101769215
Informations de publication
Date de publication:
12 02 2021
12 02 2021
Historique:
entrez:
5
3
2021
pubmed:
6
3
2021
medline:
6
3
2021
Statut:
ppublish
Résumé
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, its effects on immunity remain unclear. We used a hepcidin mimetic and several genetic models to examine the effect of low iron availability on T cells We show that low serum iron (hypoferremia), caused by increased hepcidin, severely impairs effector and memory responses to immunizations. The intensified metabolism of 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. Hypoferremia, 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. Medical Research Council, UK.
Sections du résumé
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, its effects on immunity remain unclear.
METHODS
We used a hepcidin mimetic and several genetic models to examine the effect of low iron availability on T cells
FINDINGS
We show that low serum iron (hypoferremia), caused by increased hepcidin, severely impairs effector and memory responses to immunizations. The intensified metabolism of 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
Hypoferremia, 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.
FUNDING
Medical Research Council, UK.
Identifiants
pubmed: 33665641
doi: 10.1016/j.medj.2020.10.004
pii: S2666-6340(20)30021-0
pmc: PMC7895906
doi:
Substances chimiques
Hepcidins
0
Iron
E1UOL152H7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
164-179.e12Subventions
Organisme : Wellcome Trust
ID : 108869/Z/15/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00008/10
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12010/10
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 106917/Z/15/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 105654/Z/14/Z
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2020 The Authors.
Déclaration de conflit d'intérêts
H.D. has sat on the advisory board of Kymab, received research funding from Pfizer and La Jolla Pharmaceutical Company, and received honoraria from Pharmacosmos and Vifor. The other authors declare no competing interests.
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