Treponema pallidum Promotes the Polarization of M2 Subtype Macrophages to M1 Subtype Mediating the Apoptosis and Inhibiting the Angiogenesis of Human Umbilical Vein Endothelial Cells.

M2 macrophages were related to local immune homeostasis and maternal-fetal tolerance in normal pregnancy; whether M2 macrophages can respond to the stimulation of Treponema pallidum to mediate placental vascular inflammation injury is unclear. In this study, M2 macrophages were constructed to investigate the impact of T. pallidum on macrophage polarization and the underlying signaling pathway involved in this process, and the influence of macrophage polarization triggered by T. pallidum on the apoptosis and angiogenesis of human umbilical vein endothelial cells (HUVEC) was also explored. The results showed that M2 macrophage markers (CD206 and PPARγ) and anti-inflammatory factors (TGFβ and CCL18) were decreased, while M1 macrophage marker CD80 and inflammatory cytokines (IL1β and TNFα) were increased when M2 macrophages were treated with T. pallidum, indicating that T. pallidum promoted the polarization of M2 subtype macrophages to the M1 subtype. Moreover, T. pallidum-induced M1 macrophage polarization was found to be significantly correlated with the activation of Janus kinase 1 (JAK1) and signal transducer and activator of transcription 1 (STAT1). In addition, T. pallidum-induced M1 macrophages were found to promote apoptosis and inhibit the angiogenesis of HUVECs, and JAK1 or STAT1 inhibitors could weaken the apoptosis rate and promote the angiogenesis of HUVECs. These findings revealed that T. pallidum promoted the polarization of M2 macrophages to the M1 subtype through the JAK1-STAT1 signal pathway mediating the apoptosis and inhibiting angiogenesis of HUVECs, which may provide a possible mechanism for T. pallidum-induced adverse pregnancy outcomes.