Group B streptococcus infection induces trophoblast apoptosis

Abstract

OZLEM EQUILS, KELLY DORAN, JAMES MCGREGOR, CALVIN HOBEL, University of California, Pediatrics, Los Angeles, California, University of California, San Diego, Pediatrics, San Diego, California, University of Southern California, Obstetrics and Gynecology, Los Angeles, California, University of California, Los Angeles, Los Angeles, California OBJECTIVE: Group B streptococci (GBS) is one of the leading causes of prematurity, and neonatal infection. Here, we assessed the cytotoxic effect of GBS infection on trophoblasts. STUDY DESIGN: We used JEG3 syncytiotrophoblast and 3A first trimester cytotrophoblast cell lines and either infected them with GBS or treated them with GBS extract. In order to assess whether trophoblast invasion was necessary for GBS induced trophoblast death, we infected JEG3 cells with invasiveness associated gene (iag) mutant GBS. In order to assess the effect of B-hemolysin on GBS induced torphoblast death, we treated JEG3 cells with GBS extract obtained from B-hemolysin mutant GBS. Trophoblast death was assessed by measuring supernatant lactate dehydrogenase release. Cell invasion was assessed by microscopic examination. RESULTS: We observed that in JEG3 syncytiotrophoblast and 3A first trimester cytotrophoblast cell lines both infection with GBS and treatment with GBS cell wall extract induced cell death as compared to uninfected and media treated cells respectively. We observed that iagGBS was poorly invasive in trophoblasts as compared to wild type bacteria; however iagGBS infection was significantly cytotoxic in JEG3 trophoblast cells. We observed that treatment of JEG3 trophoblast cells with cell extract from B-hemolysin deleted mutant was not cytotoxic. CONCLUSION: Trophoblasts provide a barrier between fetal circulation and placenta. Our data suggests that GBS invades and induces trophoblast cell death; which may impair fetal-placental barrier and consequently allow bacterial penetrance into fetal circulation. GBS-induced trophoblast death may provide an alternative mechanism for GBS-pathogenesis in neonatal GBS infection as well as preterm delivery.