Exposure to Group B Streptococcus-induced chorioamnionitis alters the proteome of placental extracellular vesicles

Group B Streptococcus (GBS) is an opportunistic pathogen that can induce chorioamnionitis (CA), increasing the risk of neurodevelopmental disorders (NDDs) in the offspring. The placenta facilitates maternal-fetal communication through the release of extracellular vesicles (EVs), which may carry inflammatory molecules such as interleukin (IL)-1. Although the role of EVs in immune modulation is well established, their specific characterization in the context of GBS-induced CA has not yet been investigated. Understanding placental-derived EVs could further define how IL-1 and other inflammatory factors contribute to NDDs.

We used an established rat model of GBS-induced CA. EVs from control and GBS infected dams were isolated from placentas and characterized using nanoparticle tracking analysis and transmission electron microscopy. The protein content was assessed via mass spectrometry, followed by subsequent pathway analysis. ELISA was used to quantify cytokine levels.

GBS-infected placentas exhibited calcification and increased weight, while fetal weight decreased. Analysis of the proteome from control versus GBS placental EVs revealed distinct profiles, with many proteins involved in the innate immune response, including alarmins (S100A8/9), complement pathways, and cytokine signaling pathways. Pathway analysis highlighted IL-1α and IL-1β identified as key upstream regulators. Notably, EVs from GBS-infected males showed a 44-fold increase in intracellular IL-1β compared to controls.

These findings indicate that GBS-induced CA alters the protein content of EVs from placental cells. Our findings of increased IL-1β-associated EVs highlight the need for further investigation into the role of these cytokines from GBS-exposed placentas and their role in brain injuries leading to NDDs.