Cytoplasmic Entry Induces Fetal Wastage by Disrupting Maternal Foxp3 Regulatory T Cell-Sustained Fetal Tolerance

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Although the intracellular bacterium Listeria monocytogenes has an established predilection for disseminated infection during pregnancy that often results in spontaneous abortion or stillbirth, the specific host-pathogen interaction that dictates these disastrous complications remain incompletely defined. Herein, we demonstrate systemic maternal Listeria infection during pregnancy fractures fetal tolerance and triggers fetal wastage in a dose-dependent fashion. Listeria was recovered from the majority of concepti after high-dose infection illustrating the potential for in utero invasion. Interestingly with reduced inocula, fetal wastage occurred without direct placental or fetal invasion, and instead paralleled reductions in maternal Foxp3⁺ regulatory T cell suppressive potency with reciprocal expansion and activation of maternal fetal-specific effector T cells. Using mutants lacking virulence determinants required for in utero invasion, we establish Listeria cytoplasmic entry is essential for disrupting fetal tolerance that triggers maternal T cell-mediated fetal resorption. Thus, infection-induced reductions in maternal Foxp3⁺ regulatory T cell suppression with ensuing disruptions in fetal tolerance play critical roles in pathogenesis of immune-mediated fetal wastage.

Vyšlo v časopise: Cytoplasmic Entry Induces Fetal Wastage by Disrupting Maternal Foxp3 Regulatory T Cell-Sustained Fetal Tolerance. PLoS Pathog 8(8): e32767. doi:10.1371/journal.ppat.1002873
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002873

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