Maternal Infection By Group B Streptococcus Induces Sex-Specific Maternofetal Inflammatory Signaling Leading to Postnatal ASD-like Behaviors in Males
Objectives: Mapping out the expression profiles of cytokines and innate immune cells within GBS-infected placentas, and comparing this immune profile between male and female tissues.
Methods: Lewis dams were injected intraperitoneally on gestational day 19 with β-hemolytic serotype Ia GBS (108 CFU) or saline (control; CTL). Caesarean-sections were performed at 24 h, 48 h and 72 h post-injection to collect maternofetal tissues (placentas, maternal and fetal blood, fetal brains), and to investigate sex-specific maternofetal immune activation and prenatal brain injuries (GBS: n = 18, CTL: n = 14). Proinflammatory cytokines IL-1β, TNF-α and IL-6 were studied by ELISA and immunohistochemistry.
Results: At 24 h, no difference in titers of IL-1β, TNF-α and IL-6 in maternal sera was detected between experimental conditions. At 48 h, increased titers of IL-1β, but not TNF-α and IL-6, were detected in GBS-exposed maternal sera and GBS-exposed male placentas compared to control tissues. At 72 h, increased titers of IL-1β, TNF-α and IL-6 were detected maternal sera, male placentas, and male fetuses’ sera versus CTL tissues. At 72 h, increased levels of IL-1β, TNF-α and IL-6 were detected in GBS-exposed male versus GBS-exposed female placentas. The correlation between maternofetal inflammatory responses and fetal forebrain injuries will be characterized by ongoing studies.
Conclusions: These results suggest that IL-1β might be implicated in the induction of the male-specific forebrain injuries, and subsequent ASD-like behaviors observed in this rat model. Innovative insights into the mechanistic underpinning the pathophysiology of pathogen-induced placental injuries are needed to develop appropriate novel therapeutic interventions.