Group B Streptococcus Infection of the Human Extraplacental Membranes.

Abstract

Streptococcus agalactiae (GBS) is the leading cause of infectious neonatal morbidity and mortality in the United States. GBS infections in the gravid female reproductive tract are associated with adverse birth outcomes. The ascending pathway of infection begins with GBS colonization of the vagina, passes through the cervix and uterine cavity where it can cross the extraplacental membranes and infect the fetus. However, the mechanisms by which GBS colonizes and infects the extraplacental membranes remain poorly understood. In addition, environmental toxicant interaction with the innate immune system during pregnancy-related infections remains to be elucidated.

In the present thesis, extraplacental membranes cocultured with GBS increased secretion of the antimicrobial peptide human beta defensin (HBD)-2 and killed GBS over time (P < 0.05). Notably, a pattern of localized increased HBD-2 in the amnion of GBS-infected membranes was observed. Interleukin (IL)-1alpha and IL-1beta secreted from choriodecidual tissue was essential for stimulating HBD-2 in the amnion cells. Direct stimulation of amnion cells with live GBS, lipoteichoic acid (LTA), or lipopolysaccharide (LPS) did not increase HBD-2 release. Increases in cytokine release were GBS strain dependent (P < 0.05). GBS recovery from membranes was also GBS strain dependent, with colonizing strains persisting on the choriodecidual side of the membranes. The trichloroethylene (TCE) metabolite S-(1,2)-dichlorovinyl-L-cysteine (DCVC) significantly inhibited pathogen (LTA, LPS, and GBS)-stimulated TNF-alpha release from extraplacental membranes. Both TNF-alpha mRNA expression and protein secretion were inhibited as early as 4 h after initiating co-treatment of tissue punches with DCVC and LTA (P < 0.05). A different TCE metabolite, trichloroacetic acid (10-500 µM), failed to inhibit LTA-stimulated cytokine release from extraplacental membranes.

In summary, extraplacental membranes in culture mounted a robust immune response to GBS. Cell-to-cell signaling from the choriodecidua to the amnion was critical for GBS-stimulated HBD-2 in amnion. Host response in the extraplacental membranes was GBS strain specific. The results from the present study provide new insight into the mechanisms of host defense during GBS infection and need to be considered for future treatment and prevention strategies. In addition, pathogen-toxicant interactions should be considered in the current paradigm for increased risk for intrauterine infection.