Extracellular Granzyme B directly drives Interferon-stimulated genes expression in macrophages.

Previous research indicate MIA propagates maternal inflammation to the fetal developing brain, that manifests as increased pro-inflammatory cytokines and activation of macrophages. Our data sugests that maternal Granzyme B released by aberrant decidual NK cells can reach to the fetal brain and instigate the activation of macrophages. To determine whether Gzmb can directly impact macrophages, we co-cultured murine microglial BV-2 cells with Gzmb for 20 hours, and then performed gene expression profiling analysis. We found that GzmB exposure directly induces a unique gene signature in microglia that includes the unexpected upregulation of multiple interferon-stimulated genes (ISGs). Murine microglial BV2 cells were stimulated for 20 hours using different treatments, including Ctrl, GZMB (500 ng/ml), amniotic fluid (AF, 50 μl), and AF (50 μl) + GZMB (500 ng/ml)