Maternal Immune Activation and Interleukin 17A in the Pathogenesis of Autistic Spectrum Disorder and Why It Matters in the COVID-19 Era

Michael Carter; Sophie Casey; Gerard W O'Keeffe; Louise Gibson; Louise Gallagher; Deirdre M Murray

doi:10.3389/fpsyt.2022.823096

Maternal Immune Activation and Interleukin 17A in the Pathogenesis of Autistic Spectrum Disorder and Why It Matters in the COVID-19 Era

Front Psychiatry. 2022 Feb 17:13:823096. doi: 10.3389/fpsyt.2022.823096. eCollection 2022.

Authors

Michael Carter^{1

2

3}, Sophie Casey^{1

4}, Gerard W O'Keeffe^{1

4}, Louise Gibson^{1

2}, Louise Gallagher^{5

6}, Deirdre M Murray^{1

2}

Affiliations

¹ INFANT Research Centre, University College Cork, Cork, Ireland.
² Department of Paediatrics and Child Health, University College Cork, Cork, Ireland.
³ National Children's Research Centre, Dublin, Ireland.
⁴ Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.
⁵ Department of Psychiatry, School of Medicine, Trinity College Dublin, Dublin, Ireland.
⁶ Trinity Translational Medicine Institute, St. James's Hospital, Dublin, Ireland.

Abstract

Autism spectrum disorder (ASD) is the commonest neurodevelopmental disability. It is a highly complex disorder with an increasing prevalence and an unclear etiology. Consensus indicates that ASD arises as a genetically modulated, and environmentally influenced condition. Although pathogenic rare genetic variants are detected in around 20% of cases of ASD, no single factor is responsible for the vast majority of ASD cases or that explains their characteristic clinical heterogeneity. However, a growing body of evidence suggests that ASD susceptibility involves an interplay between genetic factors and environmental exposures. One such environmental exposure which has received significant attention in this regard is maternal immune activation (MIA) resulting from bacterial or viral infection during pregnancy. Reproducible rodent models of ASD are well-established whereby induction of MIA in pregnant dams, leads to offspring displaying neuroanatomical, functional, and behavioral changes analogous to those seen in ASD. Blockade of specific inflammatory cytokines such as interleukin-17A during gestation remediates many of these observed behavioral effects, suggesting a causative or contributory role. Here, we review the growing body of animal and human-based evidence indicating that interleukin-17A may mediate the observed effects of MIA on neurodevelopmental outcomes in the offspring. This is particularly important given the current corona virus disease-2019 (COVID-19) pandemic as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy is a potent stimulator of the maternal immune response, however the long-term effects of maternal SARS-CoV-2 infection on neurodevelopmental outcomes is unclear. This underscores the importance of monitoring neurodevelopmental outcomes in children exposed to SARS-CoV-2-induced MIA during gestation.

Keywords: ASD; COVID-19; MIA; autism; cytokine; interleukin-17A (IL-17A); maternal immune activation.