Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands.
Danone Nutricia Research, Utrecht, Netherlands.
Front Immunol. 2021 Dec 17;12:797152. doi: 10.3389/fimmu.2021.797152. eCollection 2021.
Deoxynivalenol (DON), a highly prevalent contaminant of grain-based products, is known to induce reproductive- and immunotoxicities. Considering the importance of immune development in early life, the present study investigated the effects of perinatal DON exposure on allergy development and vaccine responsiveness in the offspring. Pregnant mice received control or DON-contaminated diets (12.5 mg/kg diet) during pregnancy and lactation. After weaning, female offspring were sensitized to ovalbumin (OVA) by oral administration of OVA with cholera toxin (CT). Male offspring were injected with Influvac vaccine. OVA-specific acute allergic skin response (ASR) in females and vaccine-specific delayed-type hypersensitivity (DTH) in males were measured upon intradermal antigen challenge. Immune cell populations in spleen and antigen-specific plasma immunoglobulins were analyzed. In female CT+OVA-sensitized offspring of DON-exposed mothers ASR and OVA-specific plasma immunoglobulins were significantly higher, compared to the female offspring of control mothers. In vaccinated male offspring of DON-exposed mothers DTH and vaccine-specific antibody levels were significantly lower, compared to the male offspring of control mothers. In both models a significant reduction in regulatory T cells, Tbet Th1 cells and Th1-related cytokine production of the offspring of DON-exposed mothers was observed. In conclusion, early life dietary exposure to DON can adversely influence immune development in the offspring. Consequently, the immune system of the offspring may be skewed towards an imbalanced state, resulting in an increased allergic immune response to food allergens and a decreased immune response to vaccination against influenza virus in these models.
脱氧雪腐镰刀菌烯醇(DON)是一种普遍存在于谷物产品中的污染物,已知其具有生殖毒性和免疫毒性。鉴于免疫在生命早期发育中的重要性,本研究调查了围产期 DON 暴露对后代过敏发展和疫苗反应性的影响。怀孕的老鼠在怀孕和哺乳期接受对照或 DON 污染的饮食(饮食 12.5 毫克/千克)。断奶后,雌性后代通过口服卵清蛋白(OVA)和霍乱毒素(CT)致敏。雄性后代接受 Influvac 疫苗注射。雌性的 OVA 特异性急性过敏皮肤反应(ASR)和雄性的疫苗特异性迟发型超敏反应(DTH)在皮内抗原挑战时测量。分析脾脏中的免疫细胞群和抗原特异性血浆免疫球蛋白。与对照母亲的后代相比,暴露于 DON 的母亲的 CT+OVA 致敏雌性后代的 ASR 和 OVA 特异性血浆免疫球蛋白显著升高。与对照母亲的后代相比,暴露于 DON 的母亲的疫苗接种雄性后代的 DTH 和疫苗特异性抗体水平显著降低。在这两种模型中,都观察到暴露于 DON 的母亲的后代调节性 T 细胞、Tbet Th1 细胞和 Th1 相关细胞因子产生的显著减少。总之,早期生命的饮食暴露于 DON 可能会对后代的免疫发育产生不利影响。因此,后代的免疫系统可能会偏向于不平衡状态,导致对食物过敏原的过敏免疫反应增加,对流感病毒疫苗的免疫反应降低。