Group B Streptococcus (GBS) is the leading cause of bacterial infections in utero and can cause preterm birth, fetal injury, stillbirth and infections in newborns. The mechanisms by which GBS causes these outcomes are largely unknown. We have previously reported that purified GBS pigment toxin causes hemolysis and cytolysis of certain immune cells such as mast cells and neutrophils, which contributes to disease. Previous studies have demonstrated GBS-induced dendritic cell (DC) death by pyroptosis, but little is known about whether this effect is mediated by the GBS pigment toxin.
DC are professional antigen presenting cells (APC) which provide a crucial link between the innate and adaptive immune systems and ensure that adequate immune responses are initiated in response to foreign antigen. Their role is especially important in maintaining healthy pregnancy.
Here, we show that GBS infection in vitro induced death in murine bone marrow-derived DC in a pigment toxin-dependent manner, as evidenced by lactate dehydrogenase (LDH) and IL-1b release. When phagocytosis was blocked by cytochalasin, DC death increased. Interestingly, stimulation of DC with purified pigment toxin in the absence of bacteria led to propidium iodide (PI) but not annexin V uptake or LDH or IL-1β release. It is possible that this discrepancy is due to DC plasma membrane repair, therefore allowing DC to resist pigment-mediated lysis. Further studies will investigate the impact of pigment toxin-induced DC death on GBS pathogenesis, as well as roles of caspase-1 and cell death signaling pathways in this process.