Streptococcus pyogenes infects human endometrium by limiting the innate immune response
Antonin Weckel, … , Céline Méhats, Agnès Fouet
Antonin Weckel, … , Céline Méhats, Agnès Fouet
Published December 15, 2020
Citation Information: J Clin Invest. 2021;131(4):e130746. https://doi.org/10.1172/JCI130746.
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Research Article Infectious disease Microbiology

Streptococcus pyogenes infects human endometrium by limiting the innate immune response

Abstract

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. Before efficient prophylactic measures were introduced, the mortality rate for mothers during childbirth was approximately 10%; puerperal fever still accounts for over 75,000 maternal deaths annually. Yet, little is known regarding the factors and mechanisms of GAS invasion and establishment in postpartum infection. We characterized the early steps of infection in an ex vivo infection model of the human decidua, the puerperal fever portal of entry. Coordinate analysis of GAS behavior and the immune response led us to demonstrate that (a) GAS growth was stimulated by tissue products; (b) GAS invaded tissue and killed approximately 50% of host cells within 2 hours, and these processes required SpeB protease and streptolysin O (SLO) activities, respectively; and (c) GAS impaired the tissue immune response. Immune impairment occurred both at the RNA level, with only partial induction of the innate immune response, and protein level, in an SLO- and SpeB-dependent manner. Our study indicates that efficient GAS invasion of the decidua and the restricted host immune response favored its propensity to develop rapid invasive infections in a gynecological-obstetrical context.

Authors

Antonin Weckel, Thomas Guilbert, Clara Lambert, Céline Plainvert, François Goffinet, Claire Poyart, Céline Méhats, Agnès Fouet

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Figure 5

Schematic representation of the initial steps of decidual invasive infection by GAS.

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Schematic representation of the initial steps of decidual invasive infec...
The successive steps are represented. 1: The decidua secretes nutrients and antimicrobial peptides (Figure 1I), promoting GAS multiplication at the tissue surface (Figure 1, C–H). 2: GAS invades the tissue in, among others, an SpeB-dependent manner, most likely through its capacity to degrade fibronectin (Figure 2, A–C). 3: GAS is phagocytosed at the surface and is present inside decidual immune cells at least 6 μm below the surface and 4 hpi, suggesting GAS may use immune decidual cells to invade the decidua (Figure 2, D and E). 4: GAS induces the death of decidual stromal and immune cells in an SLO-dependent mechanism (Figure 3). 5: GAS limits the innate immune response, impairing the response amplification (Figure 4). Decidual immune and stromal cells are represented as observed in the tissue; curved arrows = nutrients, AMP, or growth signaling factor secretion and diffusion; dotted line objects = damaged cells; dotted arrows = cytokine secretion.