PDF(Pubmed)
Abstract：
Recalcitrant staphylococcal osteomyelitis may be due, in part, to the ability of Staphylococcus aureus to invade bone cells. However, osteoclasts and osteoblasts are now recognized to shape host responses to bacterial infection and we have recently described their ability to produce IFN-β following S. aureus infection and limit intracellular bacterial survival/propagation. Here, we have investigated the ability of novel, rationally designed, nucleic acid nanoparticles (NANPs) to induce the production of immune mediators, including IFN-β, following introduction into bone cells. We demonstrate the successful delivery of representative NANPs into osteoblasts and osteoclasts via endosomal trafficking when complexed with lipid-based carriers. Their delivery was found to differentially induce immune responses according to their composition and architecture via discrete cytosolic pattern recognition receptors. Finally, the utility of this nanoparticle technology was supported by the demonstration that immunostimulatory NANPs augment IFN-β production by S. aureus infected bone cells and reduce intracellular bacterial burden.
摘要：
顽固性葡萄球菌骨髓炎可能是由于，在某种程度上,金黄色葡萄球菌侵入骨细胞的能力。然而,破骨细胞和成骨细胞现在被认为可以塑造宿主对细菌感染的反应，我们最近描述了它们在金黄色葡萄球菌感染后产生IFN-β并限制细胞内细菌存活/繁殖的能力。这里,我们调查了小说的能力，合理设计，核酸纳米颗粒（NANP）诱导免疫介质的产生，包括IFN-β，在引入骨细胞之后。我们证明了当与基于脂质的载体复合时，通过内体运输将代表性的NANP成功递送到成骨细胞和破骨细胞中。发现它们的递送根据它们的组成和结构通过离散的胞质模式识别受体差异地诱导免疫应答。最后,这种纳米颗粒技术的实用性得到了以下证明的支持:免疫刺激NANPs增加了金黄色葡萄球菌感染的骨细胞的IFN-β产生并降低了细胞内细菌负荷.
