Roth-Walter Franziska
Comparative Medicine, The Interuniversity Messerli Research Institute, University of Veterinary Medicine Vienna, Medical University Vienna, University of Vienna, Vienna, Austria.
Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
Front Allergy. 2022 May 10;3:859922. doi: 10.3389/falgy.2022.859922. eCollection 2022.
Although iron is one of the most abundant elements on earth, about a third of the world's population are affected by iron deficiency. Main drivers of iron deficiency are beside the chronic lack of dietary iron, a hampered uptake machinery as a result of immune activation. Macrophages are the principal cells distributing iron in the human body with their iron restriction skewing these cells to a more pro-inflammatory state. Consequently, iron deficiency has a pronounced impact on immune cells, favoring Th2-cell survival, immunoglobulin class switching and primes mast cells for degranulation. Iron deficiency during pregnancy increases the risk of atopic diseases in children, while both children and adults with allergy are more likely to have anemia. In contrast, an improved iron status seems to protect against allergy development. Here, the most important interconnections between iron metabolism and allergies, the effect of iron deprivation on distinct immune cell types, as well as the pathophysiology in atopic diseases are summarized. Although the main focus will be humans, we also compare them with innate defense and iron sequestration strategies of microbes, given, particularly, attention to catechol-siderophores. Similarly, the defense and nutritional strategies in plants with their inducible systemic acquired resistance by salicylic acid, which further leads to synthesis of flavonoids as well as pathogenesis-related proteins, will be elaborated as both are very important for understanding the etiology of allergic diseases. Many allergens, such as lipocalins and the pathogenesis-related proteins, are able to bind iron and either deprive or supply iron to immune cells. Thus, a locally induced iron deficiency will result in immune activation and allergic sensitization. However, the same proteins such as the whey protein beta-lactoglobulin can also transport this precious micronutrient to the host immune cells (holoBLG) and hinder their activation, promoting tolerance and protecting against allergy. Since 2019, several clinical trials have also been conducted in allergic subjects using holoBLG as a food for special medical purposes, leading to a reduction in the allergic symptom burden. Supplementation with nutrient-carrying lipocalin proteins can circumvent the mucosal block and nourish selectively immune cells, therefore representing a new dietary and causative approach to compensate for functional iron deficiency in allergy sufferers.
尽管铁是地球上含量最丰富的元素之一，但全球约三分之一的人口受到缺铁的影响。缺铁的主要原因除了长期饮食中铁缺乏外，还有免疫激活导致的铁吸收机制受阻。巨噬细胞是人体中分布铁的主要细胞，铁限制会使这些细胞向更促炎的状态转变。因此，缺铁对免疫细胞有显著影响，有利于Th2细胞存活、免疫球蛋白类别转换，并使肥大细胞做好脱颗粒准备。孕期缺铁会增加儿童患特应性疾病的风险，而患有过敏症的儿童和成人都更易患贫血。相反，改善铁状态似乎能预防过敏的发生。在此，总结了铁代谢与过敏之间最重要的相互联系、铁缺乏对不同免疫细胞类型的影响以及特应性疾病的病理生理学。尽管主要关注对象是人类，但我们也将其与微生物的固有防御和铁螯合策略进行比较，特别关注儿茶酚铁载体。同样，植物中通过水杨酸诱导系统获得抗性的防御和营养策略也将详细阐述，这会进一步导致类黄酮以及病程相关蛋白的合成，因为这两者对于理解过敏性疾病的病因都非常重要。许多过敏原，如脂质运载蛋白和病程相关蛋白，能够结合铁并剥夺或为免疫细胞提供铁。因此，局部诱导的缺铁会导致免疫激活和过敏致敏。然而，同样的蛋白质，如乳清蛋白β-乳球蛋白，也可以将这种珍贵的微量营养素转运到宿主免疫细胞（全乳球蛋白）并抑制其激活，促进耐受性并预防过敏。自2019年以来，也在过敏受试者中进行了多项临床试验，使用全乳球蛋白作为特殊医学用途食品，导致过敏症状负担减轻。补充携带营养物质的脂质运载蛋白可以绕过黏膜屏障，有选择地滋养免疫细胞，因此代表了一种新的饮食和病因学方法来弥补过敏患者的功能性缺铁。
