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

Pablo Garcia-Valtanen; Bianca A van Diermen; Nerissa Lakhan; Erin L Lousberg; Sarah A Robertson; John D Hayball; Kerrilyn R Diener

doi:10.1111/aji.13260

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

Am J Reprod Immunol. 2020 Aug;84(2):e13260. doi: 10.1111/aji.13260. Epub 2020 May 26.

Authors

Pablo Garcia-Valtanen¹, Bianca A van Diermen^{1

2}, Nerissa Lakhan^{1

2}, Erin L Lousberg^{1

2}, Sarah A Robertson², John D Hayball^{1

2}, Kerrilyn R Diener^{1

2}

Affiliations

¹ Experimental Therapeutics Laboratory, School of Pharmacy and Medical Science, UniSA Cancer Research Institute, University of South Australia, Adelaide, SA, Australia.
² Robinson Research Institute and Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia.

PMID: 32365239
DOI: 10.1111/aji.13260

Abstract

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.

Keywords: behavioural responses; cytokine expression profile; maternal immune activation; poly(I:C).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Autism Spectrum Disorder / immunology*
Autism Spectrum Disorder / psychology
Behavior, Animal
Child of Impaired Parents
Disease Models, Animal
Female
Humans
Immune System Diseases / immunology*
Immune System Diseases / psychology
Immunity
Immunity, Maternally-Acquired
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Poly I-C / immunology*
Pregnancy / immunology*
Prenatal Exposure Delayed Effects / immunology*
Prenatal Exposure Delayed Effects / psychology
Toll-Like Receptor 3 / genetics
Transcriptome / immunology
Virus Diseases / immunology*
Virus Diseases / psychology

Substances

TLR3 protein, mouse
Toll-Like Receptor 3
Poly I-C