Maternal host responses to poly(I:C) during pregnancy leads to both dysfunctional immune profiles and altered behaviour in the offspring

Problem: Autism spectrum disorder (ASD)-like phenotypes in murine models are linked to elevated proinflammatory cytokine profiles caused by maternal immune activation (MIA) but whether MIA alters the immune response in the offspring remains unclear. Method of Study: Polyinosinic:polycytidylic acid (poly:[IC]) was used to induce MIA in immunocompetent and control TLR3-deficient pregnant mice and cytokine levels were measured in maternal and fetal organs. Furthermore, cytokines and behaviour responses were tested after challenge with lipopolysaccharide in 7-day-old and adult mice. Results: MIA induced on E12 resulted in changes in the cytokine expression profile in maternal and fetal organs and correlated with TNFα and IL-18 dysregulation in immune organs and brains from neonatal mice born to MIA-induced dams. Such changes further correlated with altered behavioural responses in adulthood. Conclusion: MIA induced by pathogens during pregnancy can interfere with the development of the fetal immune and nervous systems leading to dysfunctional immune responses and behaviour in offspring.Pablo Garcia-Valtanen, Bianca A. van Diermen, Nerissa Lakhan, Erin L. Lousberg, Sarah A. Robertson, John D. Hayball, Kerrilyn R. Diene