Activation of the IL-1β/CXCL1/MMP-10 axis in chorioamnionitis induced by inactivated Group B Streptococcus

- GBS-induced chorioamnionitis is associated to IL-1/CINC-1-driven PMN infiltration, MMP-10 release, and IL-1 secretion within the fetus blood.
- IL-1 is likely the key player in the onset of chorioamnionitis to be targeted in future placento-protective strategies.
- This results pave the way toward targeted anti-inflammatory treatments to protect the placenta and associated multi-organ threats.

Infection or inflammation during pregnancy is known to lead to maternal immune activation triggering a fetal inflammatory response syndrome associated with deleterious effects, such as brain injury and neurodevelopmental disabilities. Group B Streptococcus (GBS) - one of the most common bacterium colonizing pregnant women - can be responsible for chorioamnionitis. Given that interleukin (IL)-1β has a major role in anti-GBS host defense, we hypothesized that IL-1β-driven innate immune response is implicated in GBS-induced chorioamnionitis. Using a rat model of GBS-induced chorioamnionitis, this study showed that inflammatory response to this pathogen was associated with maternal and placental IL-1β hyper expression. Following placental chemokine (C-X-C motif) ligand 1 (CXCL1) production, polymorphonuclear leukocytes (PMN) placental infiltration started at 24 h post-GBS exposure, and MMP-10 was released within these placentas. At 72 h, PMN infiltration extended to membranes and to membranes' arteries. This was associated with IL-1β release within the fetus blood at 72 h. Such a GBS-associated inflammatory cascade might be deleterious for fetal organs. These results pave the way toward targeted placento-protective anti-inflammatory strategies against GBS-induced chorioamnionitis.