Research progress on neutrophil extracellular traps in oral infectious diseases

Abstract

<p>Eutrophils are the first innate immune cells to reach the site of inflammation. Neutrophils produce neutro⁃ phil extracellular traps (NETs) that can quickly capture and limit the spread of pathogens, facilitating the removal of pathogens and their debris. Neutrophils in the oral cavity are specifically transformed from circulating neutrophils in the blood, and the number of NETs released by oral neutrophils is much higher than that of circulating neutrophils, thus bet⁃ ter maintaining the balance of the oral microenvironment. As a bimorphic fungus, only the mycelium phase of Candida albicans can induce NETs, which is related to the neutrophils' ability to sense the size of pathogenic microorganisms through neutrophil elastase. However, spherical Staphylococcus aureus are much smaller than Candida albicans, and they can still induce NETs. Porphyromonas gingivalis, as one of the microorganisms in the periodontitis complex, induc⁃ es fewer NETs than Streptococcus oralis and Actinomycetes, which are two common oral microorganisms, and there may be a mechanism allowing them to escape neutrophilic immunity in the early stage of periodontitis. Although the two main pathways of NET production have been studied in detail, the mechanisms involved in the induction of NETs by dif⁃ ferent microorganisms, especially from oral neutrophils, are not well understood. This review describes the mechanism of the immune effects of pathogenic microorganisms on neutrophil NETs in the oral cavity, providing a reference for the search for therapeutic targets and the development of key drugs for treating oral infectious diseases.</p>

中性粒细胞是第一批到达炎症部位的先天免疫细胞，其产生的中性粒细胞胞外捕获网（neutrophil extracellular traps，NETs）可以快速捕获并限制病原体扩散，便于清除病原体及其碎片。口腔中的中性粒细胞是由血液中的循环中性粒细胞特异性转化而来，其释放的NETs数量远高于循环中性粒细胞，以此能以更好地维持口腔微环境的平衡。白色念珠菌作为双形态真菌，只有菌丝相能够诱导NETs，这与通过中性粒细胞弹性蛋白酶感应病原微生物大小有关，但作为形态为球状的金黄色葡萄球菌，大小远小于白色念珠菌，但仍能诱导NETs产生。牙龈卟啉单胞菌作为牙周炎复合体之一的微生物，对NETs的诱导作用小于口腔链球菌和放线菌这两种口腔常见微生物，可能存在逃避中性粒细胞免疫的机制。尽管目前对NETs产生的两种主要途径有较多研究，但不同微生物诱导中性粒细胞（特别是口腔中性粒细胞）的机制并不明晰。本文就口腔中病原微生物对中性粒细胞产生NETs的免疫效应作用机制进行综述，为找寻口腔感染性疾病的治疗靶点和关键药物的研发提供参考。