Roles of Fetal Brain and Maternal Immunity in Cytomegalovirus-Related Neurodevelopmental Pathogenesis
Sarah Tarhini
Equipe “Trouble du développement cortical »

Résumé
Congenital cytomegalovirus (CMV) infection is a leading cause of human neurodevelopmental disorders, yet effective treatments are lacking and its neuropathogenesis remains poorly understood. Evidence from rodent and human studies implicates early brain immune alterations in this process. During the first part of my PhD, we targeted these early events in a rat model of CMV infection of the fetal brain. We demonstrated that maternal aspirin intake normalized CMV-induced cyclooxygenase-1 (Cox-1) overexpression in fetal microglia, improved postnatal survival and neurological outcomes, and prevented both epileptic seizures in vivo and epileptiform activities ex vivo. These effects likely involved Cox-1-dependent and independent mechanisms. In the second part, we explored whether modulating maternal immunity through maternal immune activation (MIA) could impact fetal CMV outcomes. Indeed, prior MIA influenced offspring CMV-driven neurological deficits, with bulk RNA sequencing revealing modified responses of fetal microglia to CMV infection. Together, these findings show that CMV-induced neurodevelopmental alterations can be modulated during pregnancy either by early maternal administration of anti-inflammatory drugs targeting fetal microglia, or by stimulating maternal immunity prior to fetal brain infection to induce microglial immune memory. The latter reveals that prior MIA not only preconditioned fetal microglial responses to subsequent CMV infection of the fetal brain but also influenced CMV-related postnatal outcomes.

Jury
Sonia GAREL Rapporteuse, Ibens, Cirb – Collège de France, Paris
Pierre GRESSENS Rapporteur, NeuroDiderot, Université Paris Diderot
Etienne AUDINAT Examinateur, IGF, Université de Montpellier
Hélène HIRBEC Examinatrice, IGF, Université de Montpellier
Christophe PORCHER Président du jury, Inmed, Marseille
Pierre SZEPETOWSKI Directeur de these, Inmed, Marseille
Sylvian BAUER Co-directeur de these, Inmed, Marseille

Mercredi 17 décembre 2025 à 14h – salle de conférence de l’Inmed