Toll-like receptor 9 signaling regulates tissue factor and tissue factor pathway inhibitor expression in human endothelial cells and coagulation in mice.

Objective: Bacterial DNA (CpG DNA) persists in tissues and blood under pathological conditions that are associated with enhanced intravascular coagulation. Toll-like receptor 9 recognizes CpG DNA and elicits innate and adoptive immunity, yet the impact of CpG DNA on coagulation has not been studied. In this study, we investigated the effects of CpG DNA on the expression and activity of tissue factor, a key initiator of coagulation and tissue factor pathway inhibitor in human coronary artery endothelial cells and on coagulation in mice.

Toll-like receptor 9 signaling delays neutrophil apoptosis by increasing transcription of Mcl-1.

Neutrophils detect bacterial constituents, including bacterial DNA (CpG DNA), which elicits innate immunity and prolongs the functional life span of neutrophils through suppression of apoptosis. Both the anti-apoptotic protein Mcl-1 and activation of NF-κB have been implicated in neutrophil survival, but there is no evidence that these are linked in neutrophils. We hypothesized that CpG DNA could simultaneously activate these pathways.