Sex-specific maternofetal innate immune responses triggered by group B Streptococci

Group B Streptococcus (GBS) is one of the most common bacteria isolated in human chorioamnionitis, which is a major risk factor for premature birth and brain injuries. Males are at greater risk than females for developing lifelong neurobehavioural disorders, although the origins of this sex bias remain poorly understood. We previously showed that end-gestational inflammation triggered by GBS led to early neurodevelopmental impairments mainly in the male rat progeny. Identifying key inflammatory players involved in maternofetal immune activation by specific pathogens is critical to develop appropriate novel therapeutic interventions. We aimed to map out the GBS-induced profile of innate immune biomarkers in the maternal-placental-fetal axis, and to compare this immune profile between male and female tissues. We describe here that the GBS-induced immune signalling involved significantly higher levels of interleukin (IL)-1β, cytokine-induced neutrophil chemoattractant-1 (CINC-1/CXCL1) and polymorphonuclear cells (PMNs) infiltration in male compared to female maternofetal tissues. Although male - but not female - fetuses presented increased levels of IL-1β, fetuses from both sexes in-utero exposed to GBS had increased levels of TNF-α in their circulation. Levels of IL-1β detected in fetal sera correlated positively with the levels found in maternal circulation. Here, we report for the first time that the maternofetal innate immune signalling induced by GBS presents a sexually dichotomous profile, with more prominent inflammation in males than females. These sex-specific placental and fetal pro-inflammatory responses are in keeping with the higher susceptibility of the male population for preterm birth, brain injuries and neurodevelopmental disorders such as cerebral palsy and autism spectrum disorders.