Schimmer Simone, Sridhar Vaasudevan, Satan Zelal, Grebe Anton, Saad Mohamed, Wagner Bernd, Kahlert Nele, Werner Tanja, Richter Dana, Dittmer Ulf, Sutter Kathrin, Littwitz-Salomon Elisabeth
Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Institute for the Research on HIV and AIDS-associated Diseases, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Front Immunol. 2025 Jan 14;15:1526197. doi: 10.3389/fimmu.2024.1526197. eCollection 2024.
Natural killer (NK) cells are innate immune cells that play a crucial role as a first line of defense against viral infections and tumor development. Iron is an essential nutrient for immune cells, but it can also pose biochemical risks such as the production of reactive oxygen species. The importance of iron for the NK cell function has gained increasing recognition. We have previously shown that NK cells require iron to efficiently eliminate virus-infected target cells; however, the impact of nutritional iron deficiency on NK cell function and the therapeutic benefits of iron supplementation remain unclear. Here, we demonstrate that diet-related low iron levels lead to increased retroviral loads due to functional NK cell impairment, while iron supplementation enhances NK cell proliferation, as well as their cytotoxic efficacy. Notably, iron-treated NK cells exhibited significant metabolic changes, including mitochondrial reorganization. Interestingly, although iron supplementation decreased the NK cell's cytokine production, it significantly improved NK cell degranulation and the expression of cytotoxicity-associated proteins. These findings highlight the critical role of iron in maintaining NK cell immunity and suggest that iron supplementation may hold therapeutic potential for supporting the treatment of viral infections and immunodeficiency disorders.
自然杀伤（NK）细胞是先天性免疫细胞，作为抵御病毒感染和肿瘤发展的第一道防线发挥着关键作用。铁是免疫细胞必需的营养素，但它也可能带来生化风险，如产生活性氧。铁对NK细胞功能的重要性已得到越来越多的认可。我们之前已经表明，NK细胞需要铁来有效消除病毒感染的靶细胞；然而，营养性缺铁对NK细胞功能的影响以及补铁的治疗益处仍不清楚。在这里，我们证明与饮食相关的低铁水平会由于功能性NK细胞损伤导致逆转录病毒载量增加，而补铁可增强NK细胞增殖及其细胞毒性功效。值得注意的是，经铁处理的NK细胞表现出显著的代谢变化，包括线粒体重组。有趣的是，尽管补铁会降低NK细胞的细胞因子产生，但它显著改善了NK细胞脱颗粒以及细胞毒性相关蛋白的表达。这些发现突出了铁在维持NK细胞免疫中的关键作用，并表明补铁可能具有支持病毒感染和免疫缺陷疾病治疗的潜在治疗价值。
