Hepcidin-Mediated Hypoferremia Disrupts Immune Responses to Vaccination and Infection.
Hepcidin-Mediated Hypoferremia Disrupts Immune Responses to Vaccination and Infection.
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DOI：
10.1016/j.medj.2020.10.004
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发表时间：
2021-02-12
期刊：
影响因子：
--
通讯作者：
Drakesmith H
中科院分区：
文献类型：
--
作者：
Frost JN;Tan TK;Abbas M;Wideman SK;Bonadonna M;Stoffel NU;Wray K;Kronsteiner B;Smits G;Campagna DR;Duarte TL;Lopes JM;Shah A;Armitage AE;Arezes J;Lim PJ;Preston AE;Ahern D;Teh M;Naylor C;Salio M;Gileadi U;Andrews SC;Dunachie SJ;Zimmermann MB;van der Klis FRM;Cerundolo V;Bannard O;Draper SJ;Townsend ARM;Galy B;Fleming MD;Lewis MC;Drakesmith H
特定的营养物质如何影响适应性免疫是广泛关注的问题。铁缺乏症是世界范围内最常见的微量营养素缺乏症，并造成全球疾病的重大负担;然而，其对免疫力的影响仍不清楚。我们使用铁调素模拟物和几种遗传模型来研究低铁可用性对体外T细胞以及对小鼠疫苗和病毒感染的免疫应答的影响。我们研究了由突变体TMPRSS 6引起的铁调素升高和血清铁降低的人类患者的体液免疫。我们测试了补铁对仔猪（一种天然缺铁模型）疫苗诱导的体液免疫的影响。我们表明，低血清铁（低铁血症），增加铁调素引起的，严重损害效应和记忆免疫反应。活化淋巴细胞的强化代谢需要增强铁获得的支持，这是由IRP 1/2和TFRC促进的。因此，提供额外的铁改善了低铁血症小鼠和仔猪对疫苗接种的反应，而相反，铁调素长期增加的低铁血症人具有降低的特定病原体的抗体浓度。低铁血症削弱了小鼠对流感病毒感染的T细胞、B细胞和中和抗体反应，使病毒持续存在并加剧肺部炎症和发病率。低铁血症是一种对感染的先天性生理反应，可抑制获得性免疫的发展。这种营养权衡与理解和改善在缺铁和炎症性疾病的全球共同背景下对感染和疫苗的免疫反应有关。医学研究理事会，英国铁调素引起的低血清铁损害原发性和记忆性免疫反应活化的T细胞需要铁，铁缺乏抑制线粒体代谢突变型TMPRSS 6患者具有高铁调素和较低的抗病原体IgG在病毒感染期间高铁调素抑制T和B细胞并使疾病发炎缺铁在人类和动物中非常常见。Frost等人证明，由hepcidin激素引起的血清中低浓度的铁会抑制身体对疫苗和感染的反应;相反，增加铁可以提高免疫力。缺铁在人类和动物中很常见。Frost等人研究表明，由铁调素激素引起的血清铁浓度低，会抑制身体对疫苗和感染的反应;相反，增加铁可以提高免疫力。
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 in vitro and on immune responses to vaccines and viral infection in mice. We examined humoral 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. 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 Low serum iron caused by hepcidin impairs primary and memory immune responses Activated T-cells demand iron and iron scarcity inhibits mitochondrial metabolism Patients with mutant TMPRSS6 have high hepcidin and lower IgG against pathogens High hepcidin during viral infection inhibits T- and B-cells and inflames disease 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. 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.
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激活表型，而不是中心或效应子内存表型，可预测记忆CD8+ T细胞的回忆功效。
影响因子：
15.3
作者：
Hikono, Hirokazu;Kohlmeier, Jacob E.;Takamura, Shiki;Wittmer, Susan T.;Roberts, Alan D.;Woodland, David L.
通讯作者：
Woodland, David L.
影响因子：
30.3
作者：
Arezes J;Jung G;Gabayan V;Valore E;Ruchala P;Gulig PA;Ganz T;Nemeth E;Bulut Y
通讯作者：
Bulut Y
影响因子：
10.1
作者：
Armitage, Andrew E.;Agbla, Schadrac C.;Kwambana-Adams, Brenda Anna
通讯作者：
Kwambana-Adams, Brenda Anna
影响因子：
11.8
作者：
Hefele, Lisa;Syphan, Sengdavanh;Black, Antony P.
通讯作者：
Black, Antony P.
影响因子：
32.4
作者：
Gerlach, Carmen;Moseman, E. Ashley;Loughhead, Scott M.;Alvarez, David;Zwijnenburg, Anthonie J.;Waanders, Lisette;Garg, Rohit;de la Torre, Juan C.;von Andrian, Ulrich H.
通讯作者：
von Andrian, Ulrich H.