Oral Biology, School of Dentistry, College of Medical and Dental Sciences, Edgbaston, Birmingham, UK.
Oral Biology, School of Dentistry, College of Medical and Dental Sciences, Edgbaston, Birmingham, UK.
J Endod. 2017 Sep;43(9S):S87-S94. doi: 10.1016/j.joen.2017.06.011.
The balance between the immune/inflammatory and regenerative responses in the diseased pulp is central to the clinical outcome, and this response is unique within the body because of its tissue site. Cariogenic bacteria invade the dentin and pulp tissues, triggering molecular and cellular events dependent on the disease stage. At the early onset, odontoblasts respond to bacterial components in an attempt to protect the tooth's hard and soft tissues and limit disease progression. However, as disease advances, the odontoblasts die, and cells central to the pulp core, including resident immune cells, pulpal fibroblasts, endothelial cells, and stem cells, respond to the bacterial challenge via their expression of a range of pattern recognition receptors that identify pathogen-associated molecular patterns. Subsequently, recruitment and activation occurs of a range of immune cell types, including neutrophils, macrophages, and T and B cells, which are attracted to the diseased site by cytokine/chemokine chemotactic gradients initially generated by resident pulpal cells. Although these cells aim to disinfect the tooth, their extravasation, migration, and antibacterial activity (eg, release of reactive oxygen species [ROS]) along with the bacterial toxins cause pulp damage and impede tissue regeneration processes. Recently, a novel bacterial killing mechanism termed neutrophil extracellular traps (NETs) has also been described that uses ROS signaling and results in cellular DNA extrusion. The NETs are decorated with antimicrobial peptides (AMPs), and their interaction with bacteria results in microbial entrapment and death. Recent data show that NETs can be stimulated by bacteria associated with endodontic infections, and they may be present in inflamed pulp tissue. Interestingly, some bacteria associated with pulpal infections express deoxyribonuclease enzymes, which may enable their evasion of NETs. Furthermore, although NETs aim to localize and kill invading bacteria using AMPs and histones, limiting the spread of the infection, data also indicate that NETs can exacerbate inflammation and their components are cytotoxic. This review considers the potential role of NETs within pulpal infections and how these structures may influence the pulp's vitality and regenerative responses.
牙髓病变中免疫/炎症反应与再生反应之间的平衡是临床疗效的关键，由于其组织部位的特殊性，这种反应在体内是独一无二的。致龋细菌侵入牙本质和牙髓组织，引发依赖于疾病阶段的分子和细胞事件。在疾病早期，成牙本质细胞对细菌成分作出反应，试图保护牙齿的硬组织和软组织，并限制疾病的进展。然而，随着疾病的进展，成牙本质细胞死亡，牙髓核心的细胞，包括固有免疫细胞、牙髓成纤维细胞、内皮细胞和干细胞，通过其表达一系列识别病原体相关分子模式的模式识别受体来对细菌的挑战作出反应。随后，一系列免疫细胞类型（包括中性粒细胞、巨噬细胞和 T 细胞和 B 细胞）的募集和激活发生，这些细胞最初由固有牙髓细胞产生的细胞因子/趋化因子趋化梯度吸引到病变部位。尽管这些细胞旨在对牙齿进行消毒，但它们的渗出、迁移和抗菌活性（例如，活性氧物质 [ROS] 的释放）以及细菌毒素会导致牙髓损伤并阻碍组织再生过程。最近，还描述了一种称为中性粒细胞胞外诱捕网（NETs）的新型细菌杀伤机制，该机制利用 ROS 信号并导致细胞 DNA 挤出。NETs 被抗菌肽（AMPs）装饰，它们与细菌的相互作用导致微生物捕获和死亡。最近的数据表明，与牙髓感染相关的细菌可以刺激 NETs，并且它们可能存在于发炎的牙髓组织中。有趣的是，一些与牙髓感染相关的细菌表达脱氧核糖核酸酶酶，这可能使它们能够逃避 NETs。此外，尽管 NETs 旨在使用 AMPs 和组蛋白定位和杀死入侵细菌，从而限制感染的传播，但数据还表明 NETs 会加剧炎症，并且其成分具有细胞毒性。本综述考虑了 NETs 在牙髓感染中的潜在作用以及这些结构如何影响牙髓的活力和再生反应。
