TY - JOUR
T1 - Exposure to Deoxynivalenol During Pregnancy and Lactation Enhances Food Allergy and Reduces Vaccine Responsiveness in the Offspring in a Mouse Model
AU - Seyed Toutounchi, Negisa
AU - Braber, Saskia
AU - van’t Land, Belinda
AU - Thijssen, Suzan
AU - Garssen, Johan
AU - Kraneveld, Aletta D.
AU - Folkerts, Gert
AU - Hogenkamp, Astrid
N1 - Funding Information:
The authors would like to thank Prescilla Jeurink for her helpful contribution to discussions.
Publisher Copyright:
Copyright © 2021 Seyed Toutounchi, Braber, van’t Land, Thijssen, Garssen, Kraneveld, Folkerts and Hogenkamp.
PY - 2021/12/17
Y1 - 2021/12/17
N2 - 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.
AB - 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.
KW - Deoxynivalenol
KW - developmental immunotoxicity
KW - food allergy
KW - lactation
KW - pregnancy
KW - vaccination
UR - http://www.scopus.com/inward/record.url?scp=85122083837&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2021.797152
DO - 10.3389/fimmu.2021.797152
M3 - Article
AN - SCOPUS:85122083837
SN - 1664-3224
VL - 12
SP - 1
EP - 15
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 797152
ER -