Porphyromonas gingivalis outer membrane vesicles prevent the induction of tolerogenic dendritic cells by first trimester trophoblast cells.

INTRODUCTION

Periodontitis is a risk factor for adverse pregnancy outcomes, yet the mechanisms linking Porphyromonas gingivalis (Pg) to placental immune dysregulation remain unclear. Outer membrane vesicles (OMV) derived from this pathogen act as systemic virulence mediators, but their impact on maternal-fetal immune tolerance is unknown. Dendritic cells play a central role in integrating trophoblast-derived signals to maintain immune homeostasis during early pregnancy; therefore, we investigated whether PgOMV reprogram trophoblast immunomodulatory function and thereby affect monocyte recruitment and dendritic cell differentiation.

METHODS

First-trimester trophoblast cell line was exposed to PgOMV, and conditioned media were used to evaluate monocyte migration and dendritic cell differentiation in vitro.

RESULTS

PgOMV priming increased granulocyte-macrophage colony-stimulating factor and C-C motif chemokine ligand 2 expression and enhanced monocyte migration. While Tb CM impaired monocyte-to-dendritic cell differentiation and promoted a tolerogenic phenotype characterized by low CD86 expression, increased interleukin-10 production and a higher IL-10/TNF-α ratio, PgOMV exposure abrogated this regulatory program and restored inflammatory maturation, including responsiveness to lipopolysaccharide.

DISCUSSION: These findings demonstrate that PgOMV reprogram trophoblast secretory activity, disrupt tolerogenic dendritic cell differentiation and provide a mechanistic link between periodontal infection and impaired immune regulation during pregnancy.