RT Journal Article SR Electronic T1 Streptococcus pyogenes infects human endometrium by limiting its immune response JF bioRxiv FD Cold Spring Harbor Laboratory SP 713875 DO 10.1101/713875 A1 Antonin Weckel A1 Thomas Guilbert A1 Clara Lambert A1 Céline Plainvert A1 François Goffinet A1 Claire Poyart A1 Céline Méhats A1 Agnès Fouet YR 2019 UL http://biorxiv.org/content/early/2019/07/25/713875.abstract AB Group A Streptococcus (GAS), a Gram-positive human-specific pathogen yields 517,000 deaths annually worldwide, including 163,000 due to invasive infections and among them puerperal fever. GAS is their most feared etiologic agent. Puerperal fever still accounts for more than 75,000 maternal deaths annually and before the introduction of efficient prophylactic measures 10% childbirths were followed by the mother’s death. Yet little is known regarding GAS invasive infection establishment or GAS efficiency in causing postpartum infection. To characterize its early steps, we set up coordinated analyses of ex vivo infection of the human decidua, the puerperal fever portal of entry. We analyzed GAS behavior and the immune response triggered. We demonstrate that GAS (i) benefits from tissue secreted products to multiply; (ii) invades the tissue and leads to the death of half the cells within two hours via SpeB protease and Streptolysin O activities, respectively; (iii) impairs the tissue immune response. Immune impairment occurs both at the RNA level, with the induction of only a restricted immediate innate immune response, and at the protein level, in a SLO- and SpeB-dependent manner. Our study indicates that GAS efficient decidua invasion and immune response restraint favor its propensity to develop rapid invasive infections in a gynecological-obstetrical context.