Oral Microbiology and Immunology, Institute of Oral Biology, Center of Dental Medicine, University of Zürich, Plattenstrasse 11, 8032 Zürich, Switzerland.
Cytokine. 2012 Jul;59(1):124-30. doi: 10.1016/j.cyto.2012.03.016. Epub 2012 Apr 12.
Periodontitis is an inflammatory condition that destroys the tooth-supporting tissues, as a result of local bacterial infection. Aggregatibacter actinomycetemcomitans is a Gram-negative facultative anaerobic species, highly associated with aggressive periodontitis. Periodontal inflammation is dominated by cytokines of the Interleukin (IL)-1 family. Prior to their secretion by mononuclear cells, IL-1 cytokines are processed by intracellular protein complexes, known as "inflammasomes", which can sense the bacterial challenge. The aim of this study was to investigate which inflammasomes are regulated in mononuclear cells in response to A. actinomycetemcomitans. The D7SS strain and its derivative leukotoxin and cytolethal distending toxin knock-out mutant strains were used to infect human mononuclear cells at a 1:10 cell: bacteria ratio, for 3 h. The expression of various inflammasome components in the cells was investigated by TaqMan quantitative real-time polymerase chain reaction (qPCR). The expressions of NOD-like receptor protein (NLRP)1, NLRP2 and Absent In Melanoma (AIM)2 inflammasome sensors, as well as their effector Caspase-1 were not affected. However, NLRP3 was up-regulated, while NLRP6 was down-regulated. This effect was not dependent on the leukotoxin or the cytolethal distending toxin, as demonstrated by the use of specific gene knock-out mutant strains. IL-1β and IL-18 expressions were also up-regulated by the bacterial challenge. In conclusion, A. actinomycetemcomitans enhances NLRP3 and reduces NLRP6 inflammasome expression, irrespective of its major virulence factors, confirming the high pathogenic profile of this species, and providing further insights to the mechanisms of periodontal inflammation.
牙周炎是一种炎症性疾病，由于局部细菌感染，破坏了牙齿支持组织。伴放线放线杆菌是一种革兰氏阴性兼性厌氧菌，与侵袭性牙周炎高度相关。牙周炎炎症主要由白细胞介素（IL）-1 家族的细胞因子主导。在单核细胞分泌白细胞介素 1 细胞因子之前，白细胞介素 1 细胞因子由称为“炎症小体”的细胞内蛋白复合物进行加工，这些炎症小体可以感知细菌的挑战。本研究旨在研究单核细胞中哪些炎症小体在受到 A. actinomycetemcomitans 感染时被调节。使用 D7SS 株及其衍生的白细胞毒素和细胞致死性扩张毒素敲除突变株，以 1:10 的细胞：细菌比例感染人单核细胞，持续 3 小时。通过 TaqMan 定量实时聚合酶链反应（qPCR）检测细胞中各种炎症小体成分的表达。NOD 样受体蛋白（NLRP）1、NLRP2 和 Absent In Melanoma（AIM）2 炎症小体传感器的表达不受影响，但其效应 Caspase-1 不受影响。然而，NLRP3 上调，而 NLRP6 下调。通过使用特定的基因敲除突变株，证明这种效应不依赖于白细胞毒素或细胞致死性扩张毒素。细菌刺激也上调了白细胞介素-1β和白细胞介素-18 的表达。总之，A. actinomycetemcomitans 增强了 NLRP3 并降低了 NLRP6 炎症小体的表达，无论其主要毒力因子如何，这证实了该物种的高致病性特征，并为牙周炎炎症的机制提供了进一步的见解。
