Periodontitis is induced by periodontal dysbiosis characterized by the predominance of anaerobic species. TLRs constitute the classical pathway for cell activation by infection. Interestingly, the Toll/IL-1 receptor homology domain adapters initiate signaling events, leading to the activation of the expression of the genes involved in the host immune response. The aim of this study was to evaluate the effects of Porphyromonas gingivalis on the expression and protein-protein interactions among five TIR adapters (MAL, MyD88, TRIF, TRAM and SARM) in gingival epithelial cells and endothelial cells. It was observed that P. gingivalis is able to modulate the signaling cascades activated through its recognition by TLR4/2 in gingival epithelial cells and endothelial cells. Indeed, MAL-MyD88 protein-protein interactions associated with TLR4 was the main pathway activated by P. gingivalis infection. When transient siRNA inhibition was performed, cell viability, inflammation, and cell death induced by infection decreased and such deleterious effects were almost absent when MAL or TRAM were targeted. This study emphasizes the role of such TIR adapter proteins in P. gingivalis elicited inflammation and the precise evaluation of TIR adapter protein interactions may pave the way for future therapeutics in both periodontitis and systemic disease with a P. gingivalis involvement, such as atherothrombosis.

牙周炎是由以厌氧菌为主的牙周生态失调引起的。TLR 构成了通过感染激活细胞的经典途径。有趣的是，Toll/IL-1 受体同源域适配器启动信号事件，导致宿主免疫反应相关基因表达的激活。本研究的目的是评估牙龈卟啉单胞菌对牙龈上皮细胞和内皮细胞中五种 TIR 接头（MAL、MyD88、TRIF、TRAM 和 SARM）之间表达和蛋白质-蛋白质相互作用的影响。观察到P. gingivalis能够调节通过其在牙龈上皮细胞和内皮细胞中被 TLR4/2 识别而激活的信号级联。事实上，与 TLR4 相关的 MAL-MyD88 蛋白-蛋白相互作用是牙龈卟啉单胞菌感染激活的主要途径。当进行瞬时 siRNA 抑制时，感染诱导的细胞活力、炎症和细胞死亡降低，而当靶向 MAL 或 TRAM 时，这些有害影响几乎不存在。本研究强调了这种 TIR 衔接蛋白在牙龈卟啉单胞菌引起炎症中的作用，而对 TIR 衔接蛋白相互作用的精确评估可能为未来治疗牙龈卟啉单胞菌的牙周炎和全身性疾病铺平道路 参与，如动脉粥样硬化。