Maternal immune activation during gestation modulates offspring immune profiles in a nonhuman primate model
Chelsea Kelland1, Joseph Schauer1, Ana-Maria Iosif2
1Department of Internal Medicine, Division of Rheumatology, Allergy, and Clinical Immunology, University of California, Davis, USA.
Background:
Maternal Immune Activation (MIA) during pregnancy is an environmental risk factor implicated in neurodevelopmental disorders such as autism spectrum disorder and schizophrenia. While numerous studies have shown that MIA can lead to neuropathological and behavioral abnormalities in offspring, the consequences for immune system development and function are less well characterized.
Methods:
To assess the impact of MIA on offspring immune function, we utilized samples from 24 nonhuman primate (NHP) dam-infant pairs. Pregnant dams received either saline (control) or polyinosinic: polycytidylic acid [poly(I:C)] injections in the late first trimester to induce MIA. Dam sickness behaviors and immune response were monitored. Offspring immune status was assessed longitudinally by measuring plasma cytokine, chemokine, and growth factor levels at postnatal days (PND) 30, 90, and 180. Additionally, a complete blood count, including differential leukocyte counts, was performed on blood samples collected from the offspring at PND 90 to quantify immune cell profiles.
Results:
Poly(I:C)-induced MIA triggered immediate and sustained increases in antiviral pro-inflammatory and anti-inflammatory cytokines, as well as enhanced T-cell responses in NHP dams compared with saline controls. At PND 90, MIA-exposed offspring had higher total white blood cell counts (p = 0.03), monocytes (p = 0.01), neutrophils (p = 0.04), and lymphocytes (p = 0.048) compared to controls. Further, gestational MIA exposure modulated offspring cytokine profiles at PND 30, 90, and 180, as indicated by persistent changes in the plasma levels of several cytokines and chemokines associated with both the innate and adaptive immune responses, compared with saline control offspring.
Conclusions:
Our findings suggest that exposure to MIA during early gestation has a significant long-term impact on the offspring's developing immune system. These data highlight the direct connection between maternal immune perturbation during pregnancy and immune system imprinting in offspring.
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