S5 - Symposium 2

From periodontal infection to placental impairment: Neutrophils as targets of Porphyromonas gingivalis outer membrane vesicles.

Fretes, Ailén ¹ - Lara, Brenda ¹ - Calo, Guillermina ¹ - Sabbione, Florencia ² - Diaz Appella, Mateo ¹ - Vota, Daiana ¹ - Pérez Leirós, Claudia ¹ - Tribelli, Paula ¹ - Hauk, Vanesa ¹

1) Universidad de Buenos Aires—CONICET, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Buenos Aires C1428EGA, Argentina
2) Instituto de Medicina Experimental (IMEX), Academia Nacional de Medicina. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires, Argentina
Contacto: vchauk@gmail.com

Porphyromonas gingivalis (Pg), a key pathogen in periodontitis, releases outer membrane vesicles (OMVs) enriched with virulence factors that can modulate immune responses at distant sites. Periodontitis is strongly associated with adverse pregnancy outcomes, yet the mechanisms linking Pg-derived OMVs, neutrophil activation, and placental dysfunction remain poorly defined.

To gain mechanistic insights into this association, we examined the effects of Pg OMVs on neutrophil activation and their downstream impact on trophoblastic cells. We first directly stimulated neutrophils with Pg OMVs and subsequently evaluated the impact of neutrophil- derived factors on trophoblast function.

Stimulation of neutrophils with Pg OMVs resulted in a significant increase in reactive oxygen species (ROS) production, while CD11b surface expression remained unchanged. PMA induced NET formation, characterized by DNA and elastase release. The addition of OMVs led to a trend toward reduced DNA release, without affecting elastase levels. To explore indirect effects on placental function, trophoblastic cells were exposed to conditioned media from OMV-stimulated neutrophils. This resulted in reduced trophoblast migration, as determined by scratch assays, pointing to neutrophil-derived mediators as modulators of maternal–fetal interface integrity. 

Together, these results reveal a novel mechanism by which Pg OMVs indirectly impair trophoblast function through modulation of neutrophil activation states, providing insight into how periodontal infection may contribute to placental dysfunction and adverse pregnancy outcomes.