Modulation of death and inflammatory signaling in decidual stromal cells following exposure to group B streptococcus

Abstract

Group B Streptococcus (GBS) is an opportunistic bacterial pathogen that contributes to miscarriage, preterm birth, and serious neonatal infections. Studies have indicated that some multilocus sequence types (STs) of GBS are more likely to cause severe disease than others. We hypothesized that the ability of GBS to elicit varying host responses in maternal decidual tissue during pregnancy is an important factor regulating infection and disease severity. To address this hypothesis, we utilized an antibody microarray to compare changes in production and activation of host signaling proteins in decidualized telomerase-immortalized human endometrial stromal cells (dT-HESCs) following infection with GBS strains from septic neonates or colonized mothers. GBS infection increased levels of total and phosphorylated mitogen-activated protein kinase (MAPK) family members such as p38 and JNK and induced nuclear factor kappa B (NF-κB) pathway activation. Infection also altered the regulation of additional proteins that mediate cell death and inflammation in a strain-specific manner, which could be due to the observed variation in attachment to and invasion of the decidual stromal cells and ability to lyse red blood cells. Further analyses confirmed array results and revealed that p38 promotes programmed necrosis in dT-HESCs. Together, the observed signaling changes may contribute to deregulation of critical developmental signaling cascades and inflammatory responses following infection, both of which could trigger GBS-associated pregnancy complications.