Lara Brenda, Sassot Matías, Calo Guillermina, Paparini Daniel, Gliosca Laura, Chaufan Gabriela, Loureiro Iñaki, Vota Daiana, Ramhorst Rosanna, Pérez Leirós Claudia, Hauk Vanesa
Universidad de Buenos Aires-CONICET, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Buenos Aires C1428EGA, Argentina.
Universidad de Buenos Aires, Facultad de Odontología, Cátedra de Microbiología, Buenos Aires C1122AAH, Argentina.
Life (Basel). 2023 Sep 27;13(10):1971. doi: 10.3390/life13101971.
Extracellular vesicles released by the primary pathogen of periodontal disease (), referred to as outer membrane vesicles (OMVs), have been associated with the pathogenesis of systemic diseases like cardiovascular disease, rheumatoid arthritis, and Alzheimer's disease. A pathogenic role for by disrupting placental homeostasis was proposed in the association between periodontal disease and adverse pregnancy outcomes. On the basis that trophoblast-derived factors modulate endothelial and immune cell profiles in normal pregnancy and the scarce presence of in placenta, we hypothesized that OMVs from affect trophoblast cell phenotype, impairing trophoblast-endothelium and trophoblast-neutrophil interactions. By means of in vitro designs with first-trimester human trophoblast cells, endothelial cells, and freshly isolated neutrophils, we showed that OMVs are internalized by trophoblast cells and modulate the activity and expression of functional markers. Trophoblast cells primed with OMVs enhanced neutrophil chemoattraction and lost their anti-inflammatory effect. In addition, reduced migration with enhanced adhesion of monocytes was found in endothelial cells upon incubation with the media from trophoblast cells pretreated with OMVs. Taken together, the results support a pathogenic role of OMVs at early stages of pregnancy and placentation through disruption of trophoblast contribution to vascular transformation and immune homeostasis maintenance.
牙周病主要病原体释放的细胞外囊泡（），称为外膜囊泡（OMV），已被认为与心血管疾病、类风湿性关节炎和阿尔茨海默病等全身性疾病的发病机制有关。在牙周病与不良妊娠结局的关联中，有人提出通过破坏胎盘内环境稳态发挥致病作用。基于滋养层来源的因子在正常妊娠中调节内皮细胞和免疫细胞特征以及胎盘中存在少量，我们推测来自的OMV会影响滋养层细胞表型，损害滋养层-内皮细胞和滋养层-中性粒细胞相互作用。通过使用孕早期人滋养层细胞、内皮细胞和新鲜分离的中性粒细胞进行体外实验设计，我们发现滋养层细胞会内化OMV并调节功能标志物的活性和表达。用OMV预处理的滋养层细胞会增强中性粒细胞趋化作用并失去其抗炎作用。此外，用OMV预处理的滋养层细胞培养基孵育后，内皮细胞中单核细胞的迁移减少而黏附增强。综上所述，这些结果支持OMV在妊娠和胎盘形成早期通过破坏滋养层对血管转化和免疫稳态维持的作用而发挥致病作用。
