1 Department of Oral Health Sciences, KU Leuven, Leuven, Belgium.
2 Laboratory of Immunobiology, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven, University of Leuven, Leuven, Belgium.
J Dent Res. 2018 May;97(5):547-555. doi: 10.1177/0022034517752675. Epub 2018 Feb 2.
Periodontal diseases originate from a dysbiosis within the oral microbiota, which is associated with a deregulation of the host immune response. Although little is known about the initiation of dysbiosis, it has been shown that HO production is one of the main mechanisms by which some commensal bacteria suppress the outgrowth of pathobionts. Current models emphasize the critical nature of complex microbial biofilms that form unique microbial ecologies and of their change during transition from health (homeostatic) to disease (dysbiotic). However, very little is known on how this alters their virulence and host responses. The objective of this study was to determine differences in virulence gene expression by pathobionts and the inflammatory host response in homeostatic and dysbiotic biofilms originating from the same ecology. Quantitative polymerase chain reaction was performed to quantify the pathobiont outgrowth. Expression analysis of bacterial virulence and cellular inflammatory genes together with cytokine enzyme-linked immunosorbent assays were used to detect differences in bacterial virulence and to analyze potential differences in inflammatory response. An increase in pathobionts in induced dysbiotic biofilms was observed compared to homeostatic biofilms. The main virulence genes of all pathobionts were upregulated in dysbiotic biofilms. Exposure of these dysbiotic biofilms to epithelial and fibroblast cultures increased the expression of interleukin (IL)-6, IL-1β, tumor necrosis factor-α, and matrix metalloprotease 8, but especially the chemokine CXCL8 (IL-8). Conversely, homeostatic and beneficial biofilms had a minor immune response at the messenger RNA and protein level. Overall, induced dysbiotic biofilms enriched in pathobionts and virulence factors significantly increased the inflammatory response compared to homeostatic and commensal biofilms.
牙周病源于口腔微生物群落的失调，这与宿主免疫反应的失调有关。虽然对于失调的起始知之甚少，但已经表明 HO 产生是某些共生细菌抑制病原体过度生长的主要机制之一。目前的模型强调了形成独特微生物生态系统的复杂微生物生物膜的关键性质，以及它们在从健康（稳态）向疾病（失调）转变过程中的变化。然而，对于这如何改变它们的毒力和宿主反应，我们知之甚少。本研究的目的是确定源自同一生态系统的稳态和失调生物膜中病原体的毒力基因表达和炎症宿主反应的差异。通过定量聚合酶链反应来定量测定病原体的生长。细菌毒力和细胞炎症基因的表达分析以及细胞因子酶联免疫吸附测定用于检测细菌毒力的差异，并分析炎症反应的潜在差异。与稳态生物膜相比，诱导失调生物膜中的病原体数量增加。所有病原体的主要毒力基因在失调生物膜中上调。将这些失调生物膜暴露于上皮细胞和成纤维细胞培养物中，增加了白细胞介素 (IL)-6、IL-1β、肿瘤坏死因子-α 和基质金属蛋白酶 8 的表达，但特别是趋化因子 CXCL8（IL-8）。相反，稳态和有益生物膜在信使 RNA 和蛋白质水平上的免疫反应较小。总体而言，与稳态和共生生物膜相比，富含病原体和毒力因子的诱导失调生物膜显著增加了炎症反应。
