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Generating a Reproducible Model of Mid-Gestational Maternal Immune Activation using Poly(I:C) to Study Susceptibility and Resilience in Offspring
Published on: August 17, 2022
Maternal immunization programs postnatal immune responses and reduces atherosclerosis in offspring
Tomoya Yamashita1, Stefan Freigang, Claudia Eberle
1Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0682, USA.
Circulation Research
|September 2, 2006
Summary
Maternal immunization with oxidized LDL (OxLDL) before pregnancy protects offspring from atherosclerosis. This protection involves altered immune responses, not just reduced fetal exposure to high cholesterol.
Area of Science:
- Immunology
- Cardiovascular Biology
- Developmental Biology
Background:
- Maternal hypercholesterolemia during pregnancy programs offspring for atherosclerosis via oxidation-dependent mechanisms.
- Oxidized LDL (OxLDL) is implicated in atherogenesis and fetal programming.
Purpose of the Study:
- To investigate if maternal immunization with OxLDL before pregnancy protects offspring from in utero atherogenic programming.
- To explore the immunological mechanisms underlying this protective effect.
Main Methods:
- Maternal immunization of rabbits and LDL receptor-deficient mice with OxLDL before pregnancy.
- Assessment of atherosclerosis in adult offspring.
- Analysis of offspring immune responses, including antibody production and B cell activity, to OxLDL.
- Evaluation of transplacental immunoglobulin transfer.
Main Results:
- Maternal OxLDL immunization reduced offspring atherosclerosis by up to 56%.
- Protection was not solely due to reduced fetal hypercholesterolemia.
- Offspring of immunized mothers showed increased IgM antibodies to OxLDL epitopes and IgM-LDL immune complexes.
- Maternal immunization influenced offspring's B cell and antibody responses independently of transplacental immunoglobulins.
Conclusions:
- Maternal immunization with OxLDL antigens can reduce offspring atherogenesis through mechanisms beyond reduced fetal lipid exposure.
- Maternal adaptive immunity to specific antigens can modulate offspring's postnatal immune programming.
- Targeting maternal immunity offers a potential strategy for preventing immune-modulated diseases later in life.
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