Hepcidin-Mediated Hypoferremia Disrupts Immune Responses to Vaccination and Infection

Frost, J. E. F.; Tan, Tiong Kit; Abbas, Munawar; Wideman, Sarah; Bonadonna, Michael; Stoffel, Nicole U.; Wray, Katherine; Kronsteiner, Barbara; Smits, Gaby; Campagna,; Duarte, Tiago; Lopes, José Manuel; Shah, Akshay; Armitage, Andrew E.; Arezes, João; Lim, Pei Jin; Preston, Alexandra E; Ahern, David K.; Teh, Megan R; Naylor, Caitlin; Salio, Mariolina; Gileadi, Uzi; Andrews, Simon C.; Dunachie, Susanna; Zimmermann, Michael; Klis, van der; Cerundolo, Vincenzo; Bannard, Oliver; Draper, Simon J.; Arm., Townsend; Galy, Bruno; Fleming, Mark D.; Lewis, Marie; Drakesmith, Hal

doi:10.1016/j.medj.2020.10.004

Cited by 77 publications

(131 citation statements)

References 61 publications

Supporting

Mentioning

123

Contrasting

Order By: Relevance

“…Iron deficient and iron-deficient anaemic children in our study had lower immune response for MSP3 FVO antigen compared to the iron-sufficient and iron-replete study participants after receiving MNP with iron. Other findings suggested that humoral and cell-mediated immunogenic mechanisms were influenced by iron deficiency and iron deficiency anaemia resulting in their poor immunological response [27,31,[35][36][37]. Possibly, the effects of Iron deficient and irondeficient anaemia in children led to impairment on the maturation and proliferation of immune cells especially B and T-lymphocytes, thus increasing their vulnerability to other infections including malaria [31,38].…”

Section: Discussionmentioning

confidence: 99%

Impact of IgG response to malaria-specific antigens and immunity against malaria in pre-school children in Ghana. A cluster randomized, placebo-controlled trial

et al. 2021

View full text Add to dashboard Cite

Background Iron fortification and micronutrient initiatives, specifically, vitamin A, and zinc supplementation are the most cost-effective developmental strategies against malnutrition and health emergencies in pre-school children. Iron-deficiency among pre-school children have been documented, however, studies evaluating the impact of immunoglobulin G (IgG) isotype responses among iron-fortified pre-school children in malaria endemic communities has not been assessed. We evaluated the impact of iron fortification on the IgG responses to GLURP R0, GLURP R2 and MSP3 FVO malaria-specific antigens among pre-school children in malaria endemic areas. Methods This community-based, placebo-controlled, double-blinded, cluster-randomized trial study was conducted in Wenchi Municipal and Tain District of Bono Region. The trial was registered at ClinicalTrials.gov-registered trial (Identifier: NCT01001871). Ethical approval was obtained and informed consent were sought from each participant parents/guardian. For the current objective, 871 children aged 6–35 months were screened, from which 435 children received semi-liquid home-made meals mixed with 12.5 mg of iron daily (intervention group), and 436 received micronutrient powder without iron (placebo group) for 5 months. Standardized clinical and epidemiological questionnaires were administered and blood samples taken to measure IgG responses to GLURP R0, GLURP R2 and MSP3 FVO recombinant antigens using the Afro Immunoassay (AIA) protocol. Results Baseline anthropometry, malaria diagnosis, anaemia and iron status, demographic features and dietary intake were identical among the groups (p > 0.05). After the intervention, there was no significant difference in the IgG response against GLUP R0, GLUP R2 and MSP3 FVO between the iron-containing micronutrient and placebo groups (p > 0.05). The iron-containing micronutrient powder group who were iron-sufficient or iron replete had significantly higher IgG response to GLURP R0 and GLURP R2 compared to iron-deficient and iron-deficiency anaemia in the same group (p < 0.05). The IgG responses to all the three malaria specific antigens were low among children without malaria episode but high among those with two and four episodes due to exposure differences. Conclusion Iron fortification did not influence antibody response against endogenous malaria specific antigens among pre-school children in malaria endemic areas, however, IgG response to malaria specific antigens were high among children with sufficient iron status.

show abstract

Section: Discussionmentioning

confidence: 99%

Impact of IgG response to malaria-specific antigens and immunity against malaria in pre-school children in Ghana. A cluster randomized, placebo-controlled trial

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Iron levels are key to adaptive responses to pathogens and vaccines; anemia, iron or increased hepcidin and low serum iron caused by a mutation in TMPRSS6 predict reduced responses to rubella, diphtheria, pertussis, H. influenzae type B and pneumococcal vaccines [ 212 , 213 ]. Importantly, in humans another homozygous mutation in TFRC (the gene encoding TFR1) results in defective TFR1 iron internalization.…”

Section: Metals and Adaptive Immune Cells Of The Lungmentioning

confidence: 99%

Nutritional immunity: the impact of metals on lung immune cells and the airway microbiome during chronic respiratory disease

et al. 2021

View full text Add to dashboard Cite

Nutritional immunity is the sequestration of bioavailable trace metals such as iron, zinc and copper by the host to limit pathogenicity by invading microorganisms. As one of the most conserved activities of the innate immune system, limiting the availability of free trace metals by cells of the immune system serves not only to conceal these vital nutrients from invading bacteria but also operates to tightly regulate host immune cell responses and function. In the setting of chronic lung disease, the regulation of trace metals by the host is often disrupted, leading to the altered availability of these nutrients to commensal and invading opportunistic pathogenic microbes. Similarly, alterations in the uptake, secretion, turnover and redox activity of these vitally important metals has significant repercussions for immune cell function including the response to and resolution of infection. This review will discuss the intricate role of nutritional immunity in host immune cells of the lung and how changes in this fundamental process as a result of chronic lung disease may alter the airway microbiome, disease progression and the response to infection.

show abstract

“…ID in mice attenuates T-cell-dependent and -independent antigenspecific antibody responses, and impairs B-cell proliferation [80]. The intensified metabolism of activated lymphocytes requires high amounts of iron, and T-cell and B-cell responses to adenovirus and vaccinia virus are inhibited in ID mice [81]. Imposing hypoferremia blunts T cell, B cell, and neutralizing antibody responses to influenza virus infection in mice, exacerbating lung inflammation and morbidity, and iron repletion improved the response to vaccination in ID mice [81].…”

Section: Ironmentioning

confidence: 99%

“…The intensified metabolism of activated lymphocytes requires high amounts of iron, and T-cell and B-cell responses to adenovirus and vaccinia virus are inhibited in ID mice [81]. Imposing hypoferremia blunts T cell, B cell, and neutralizing antibody responses to influenza virus infection in mice, exacerbating lung inflammation and morbidity, and iron repletion improved the response to vaccination in ID mice [81]. A recent birth cohort study in Kenya has shown that ID at time of routine infant vaccination is a strong predictor of vaccine response to diphtheria, pertussis and pneumococcus [82].…”

Section: Ironmentioning

confidence: 99%

Strengthening the immunity of the Swiss population with micronutrients: A narrative review and call for action

Berger¹,

Herter-Aeberli²,

Zimmermann³

et al. 2021

Clinical Nutrition ESPEN

Self Cite

View full text Add to dashboard Cite

Background The enormous health impact of the COVID-19 pandemic has refocused attention on measures to optimize immune function and vaccine response. Dietary deficiencies of micronutrients can weaken adaptive immunity. The aim of this review was to examine links between micronutrients, immune function and COVID-19 infection, with a focus on nutritional risks in subgroups of the Swiss population. Methods Scoping review on the associations between selected micronutrients (vitamins D and C, iron, selenium, zinc, and n-3 PUFAs) and immunity, with particular reference to the Swiss population. These nutrients were chosen because previous EFSA reviews have concluded they play a key role in immunity. Results The review discusses the available knowledge on links between sufficient nutrient status, optimal immune function, and prevention of respiratory tract infections. Because of the rapid spread of the COVID-19 pandemic, controlled intervention studies of micronutrients in the context of CIOVIUD-19 infection are now underway, but evidence is not yet available to draw conclusions. The anti-inflammatory properties of n-3 PUFAs are well established. In Switzerland, several subgroups of the population are at clear risk of nutrient deficiencies; e.g., older adults, multiple comorbidities, obesity, pregnancy, and institutionalized. Low intakes of n-3 PUFA are present in a large proportion of the population. Conclusion There are clear and strong relationships between micronutrient and n-3 PUFA status and immune function, and subgroups of the Swiss population are at risk for deficient intakes. Therefore, during the COVID-19 pandemic, as a complement to a healthy and balanced diet, it may be prudent to consider supplementation with moderate doses of Vitamins C and D, as well as of Se, Zn and n-3 PUFA, in risk groups.

show abstract

Hepcidin-Mediated Hypoferremia Disrupts Immune Responses to Vaccination and Infection

Abstract: Iron deficiency is very common in humans and animals. Frost et al. demonstrate that low concentrations of iron in serum, caused by the hormone hepcidin, inhibit the body's response to vaccines and infections; conversely, increasing iron can boost immunity.

Cited by 77 publications

References 61 publications

Impact of IgG response to malaria-specific antigens and immunity against malaria in pre-school children in Ghana. A cluster randomized, placebo-controlled trial

Impact of IgG response to malaria-specific antigens and immunity against malaria in pre-school children in Ghana. A cluster randomized, placebo-controlled trial

Nutritional immunity: the impact of metals on lung immune cells and the airway microbiome during chronic respiratory disease

Strengthening the immunity of the Swiss population with micronutrients: A narrative review and call for action

Contact Info

Product

Resources

About