Moya, H. A. | bioRxiv Science

bioRxiv2025

Prenatal maternal infection promotes maternal microchimeric cells to alter infection risk in male offspring

Vertically transferred maternal cells or maternal microchimeric cells (MMCs) engraft the fetus and persist in offspring for long periods of time. How altered maternal immune states arising from infection affect MMCs and their function in offspring is poorly understood. Here, we show that pregnancy-associated transient maternal infection alters MMCs to differentially regulate immunity in offspring. In male offspring of dams previously infected with Yersinia pseudotuberculosis, MMCs confer a pro-inflammatory type 17 T effector phenotype that leads to enhanced protective immunity to an unrelated Salmonella infection. Thus, acquired maternal cells imprinted by microbial exposure during pregnancy exert an antigen agnostic and sex-differential effect on offspring immunity, and may potentially be targeted to deliver immune benefits to infants in the vulnerable early life period.

immunology↗

bioRxiv2022

Gonadal Hormones Impart Male-Biased Behavioral Vulnerabilities to Immune Activation via Microglial Mitochondrial Function

There is a strong male bias in the prevalence of many neurodevelopmental disorders such as autism spectrum disorder. However, the mechanisms underlying this sex bias remain elusive. Infection during the perinatal period is associated with an increased risk of neurodevelopmental disorder development. Here, we used a mouse model of early-life immune activation that reliably induces deficits in social behaviors only in males. We demonstrate that male-biased alterations in social behavior are dependent upon microglial immune signaling and are coupled to alterations in mitochondrial morphology, gene expression, and function specifically within microglia, the innate immune cells of the brain. Additionally, we show that this behavioral and microglial mitochondrial vulnerability to early-life immune activation is programmed by the male-typical perinatal gonadal hormone surge. These findings demonstrate that social behavior in males over the lifespan are regulated by microglia-specific mechanisms that are shaped by events that occur in early development.

neuroscience↗