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

PLoS Pathogens

Jared H. Rowe¹ 

[1] Departments of Pediatrics and Microbiology, Center for Infectious Disease and Microbiology Translational Research, University of Minnesota School of Medicine, Minneapolis, Minnesota, United States of America

关键词: Regulatory T cells;    T cells;    Immune suppression;    Listeria monocytogenes;    Pathogens;    Cytotoxic T cells;    Cell disruption;    Listeria;   

DOI  :  10.1371/journal.ppat.1002873

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY