Pregnant women are healthy carriers of mycoplasmas specifically activating the NLRP7 inflammasomes Marilyne Lavergne1, Corinne Belville1, Héléna Choltus1, Christelle Gross1, Régine Minet-Quinard1 2, Denis Gallot1 3, Vincent Sapin1 2, Loïc Blanchon1. 1 Genetics, Reproduction and Development (GReD) Laboratory, Clermont Auvergne University, CNRS UMR 6293, INSERM U1103, Translational Approach to Epithelial Injury and Repair Team, Clermont-Ferrand, France. 2 CHU Clermont-Ferrand, Medical Biochemistry and Molecular Biology Department, Clermont-Ferrand, France. 3 CHU Clermont-Ferrand, Obstetrics and Gynecology Department, Clermont-Ferrand, France. Inflammation plays a pivotal role in term and preterm fetal membranes (FM) rupture, but the detailed mechanisms remain unclear. In this context, studies on inflammasomes recently intensified. Their functions in FM begin to be described but grey areas remain. Thus, the aim of our work was to complete the characterization of inflammasomes-dependent inflammatory processes, focusing on NLRP inflammasomes. We identified two natural activators of NLRP7 inflammasomes in term human FM of healthy patients: Mycoplasma salivarium and Mycoplasma fermentans. We used the Fibroblast-Stimulating Lipopeptide-1 (FSL-1), a lipopeptide derived from a lipoprotein of M. salivarium, to study the effect of these mycoplasmas on FM cells. The stimulation of primary amnion epithelial cells with this ligand demonstrated (i) an increased protein level of the three actors of the NLRP7 inflammasome (NLRP7, ASC and pro-caspase-1), (ii) the formation of this inflammasome by NLRP7 and ASC colocalization and (iii) the activation of this inflammasome, by cleavages of two end-effectors, pro-caspase-1 and gasdermin D. These results indicate for the first time that FM are able to activate NLRP7 inflammasomes signalization in response to a pro-inflammatory signal. Further investigations are needed to decipher the involvement of M. salivarium and M. fermentans in the pathophysiology of human FM rupture. The NLRP7 inflammasomes pathway could therefore be a new potential therapeutic target to prevent premature rupture of FM.