Maternal host responses to poly(I:C) during pregnancy leads to both dysfunctional immune profiles and altered
Pablo Garcia-Valtanen1, Bianca A van Diermen1,2, Nerissa Lakhan1,2
1Experimental Therapeutics Laboratory, School of Pharmacy and Medical Science, UniSA Cancer Research Institute, University of South Australia, Adelaide, SA, Australia.
Problem:
Autism spectrum disorder (ASD)-like phenotypes in murine models are linked to elevated pro-inflammatory 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 foetal 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 foetal 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 foetal immune and nervous systems leading to dysfunctional immune responses and behaviour in offspring.
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