Vallboehmer Fynn, Schoofs Hannah, Rink Lothar, Jakobs Jana
Institute of Immunology, Faculty of Medicine, RWTH Aachen University Hospital, Pauwelsstraße 30, 52074 Aachen, Germany.
Institute of Immunology, Faculty of Medicine, RWTH Aachen University Hospital, Pauwelsstraße 30, 52074 Aachen, Germany.
Clin Nutr. 2025 Aug;51:161-173. doi: 10.1016/j.clnu.2025.06.010. Epub 2025 Jun 21.
BACKGROUND & AIMS: Sufficient zinc status is crucial for undisturbed immune function. Further, dietary zinc requirements are mainly covered by animal products. Consequently, plant-based diets have been repeatedly linked to zinc deficiency. In the light of increasing popularity of plant-based diets, elucidating the impact of zinc deficiency on the innate immune system of vegetarians and vegans is of great interest. Although it has been previously shown that interferon (IFN) -α response towards viral stimuli can be enhanced by administering zinc in vitro, the underlying molecular process remains unknown. In this project, we investigate the effect of short-term, oral zinc supplementation in vivo on antiviral immune response and describe the potential molecular mechanism behind zinc-dependent interferon-α production.
Zinc status of omnivore, vegetarian and vegan subjects was determined by serum zinc measurement and a food frequency questionnaire (FFQ). Antiviral IFN-α response was measured in whole-blood and peripheral blood mononuclear cells upon viral stimulus. Furthermore, expression of interferon regulatory factor (IRF) 3, a positive regulator of IFNα, was quantified in each cohort. If zinc deficiency was detected, participants received oral zinc supplementation and tests were repeated afterwards.
We observed a high prevalence of imminent or manifest zinc deficiency among vegetarians and vegans. Compared to omnivores, IFNα response and IRF3 levels were significantly reduced. Moreover, we were able to enhance zinc status, increase IRF3 expression and reconstitute IFNα response by oral zinc supplementation.
We identified zinc-dependent IRF3 expression as an essential cellular mechanism behind impaired IFNα response in zinc-deficient subjects. This may contribute to disturbed antiviral immunity and cause increased susceptibility to virus infections in vivo. Oral zinc supplementation effectively restored IRF3 and IFNα levels. Hence, nutritional interventions may become increasingly important in order to prevent health implications from micronutrient deficiencies among vegetarians and vegans.
充足的锌状态对于维持正常免疫功能至关重要。此外，饮食中的锌需求主要由动物产品满足。因此，以植物性食物为主的饮食模式一直与锌缺乏反复关联。鉴于以植物性食物为主的饮食模式越来越受欢迎，阐明锌缺乏对素食者和纯素食者先天免疫系统的影响具有重要意义。尽管此前已表明，体外给予锌可增强干扰素（IFN）-α对病毒刺激的反应，但其潜在分子机制仍不清楚。在本项目中，我们研究了体内短期口服补锌对抗病毒免疫反应的影响，并描述了锌依赖性干扰素-α产生背后的潜在分子机制。
通过血清锌检测和食物频率问卷（FFQ）确定杂食者、素食者和纯素食者的锌状态。在病毒刺激后，检测全血和外周血单核细胞中的抗病毒IFN-α反应。此外，对每个队列中IFNα的正向调节因子干扰素调节因子（IRF）3的表达进行定量分析。如果检测到锌缺乏，参与者接受口服补锌，之后重复进行检测。
我们观察到素食者和纯素食者中存在即将发生或明显的锌缺乏的高发生率。与杂食者相比，IFNα反应和IRF3水平显著降低。此外，我们能够通过口服补锌改善锌状态、增加IRF3表达并恢复IFNα反应。
我们确定锌依赖性IRF3表达是锌缺乏受试者中IFNα反应受损背后的一种关键细胞机制。这可能导致抗病毒免疫紊乱，并增加体内对病毒感染的易感性。口服补锌有效地恢复了IRF3和IFNα水平。因此，为预防素食者和纯素食者因微量营养素缺乏而产生的健康问题，营养干预可能变得越来越重要。
