Abstract
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.
Highlights
Pregnancy and lactation represent crucial periods in the development of the newborn’s immune system [1]
This study was conducted in accordance with institutional guidelines for the care and use of laboratory animals established by the Animal Ethics Committee of the Utrecht University, and all animal procedures related to the purpose of the research were approved under license of the national competent authority, securing full compliance the European Directive 2010/63/EU for the use of animals for scientific purposes
Results of Influvac-induced delayed-type hypersensitivity (DTH) reaction, as a model for in vivo cellular Th1 dependent immunity, showed a significant antigenspecific response to Influvac in vaccinated mice born to control mothers (Figure 3A, p
Summary
Pregnancy and lactation represent crucial periods in the development of the newborn’s immune system [1]. A wide range of contaminants present in maternal food and environment during these periods can interfere with the process of immune programming, leading to long-term or permanent changes in the offspring [1, 2]. A strong connection between developmental immunotoxicity and the elevated risk for immune related disorders has been suggested. Diseases such as childhood asthma and allergies [7], chronic otitis media, type-1 diabetes, childhood leukemia and pediatric celiac disease are all related to disturbed and imbalanced immune capacity during early stages of immune development [8]. Any prenatal or neonatal environmental factors that interfere with the immune programming in early life, can impose a risk for allergy development and diminished host resistance to disease
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