Decoding the Innate Immune Response to Group B Streptococcus Infections at the Maternal-Fetal Interface

Abstract

Bacterial infections, including Group B Streptococcus (GBS) in pregnancy are a common cause of early preterm birth and severe neonatal morbidity and mortality. The virulence factors expressed by a particular GBS strain are one important factor in determining invasion; host defenses at the maternal-fetal interface are likely equally important in clearing GBS before invasion can occur. The central hypothesis of the dissertation is that differences in immune cell composition and recruitment, expression of immune cell checkpoints, and cell death profile govern GBS infection at the maternal-fetal interface and clinical outcomes. I found that an early GBS infection would induce the expression of immune checkpoint proteins in the placental chorioamniotic membranes and decidua to counteract the cytokine and chemokine response of immune infiltration. Moreover, bacterial invasion into the amniotic fluid was associated with IL-1 signaling and inflammatory host cell death (pyroptosis, ferroptosis) at the maternal-fetal interface. In contrast, a resolved GBS infection was linked to a mild-inflammatory response of cytotoxic granules, likely produced by uterine NK cells and/or CD8+ T cells. Surprisingly, there was a prominent inflammatory signature in the uterine muscle and preterm labor rate in the resolved infection group. Future studies should focus on understanding how preterm birth therapeutics might support the function of innate immune cells in the maternal decidua to combat pathogens inducing preterm birth.