Aggregatibacter actinomycetemcomitans targets NLRP3 and NLRP6 inflammasome expression in human mononuclear leukocytes
Aggregatibacter actinomycetemcomitans targets NLRP3 and NLRP6 inflammasome expression in human mononuclear leukocytes
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DOI：
10.1016/j.cyto.2012.03.016
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发表时间：
2012-07-01
期刊：
影响因子：
3.8
通讯作者：
Johansson, Anders
中科院分区：
文献类型：
--
作者：
Belibasakis, Georgios N.;Johansson, Anders
牙周炎是一种炎症性疾病，由于局部细菌感染而破坏牙齿支持组织。伴放线聚集杆菌是一种革兰氏阴性兼性厌氧细菌，与侵袭性牙周炎密切相关。牙周炎由白细胞介素（IL）-1家族的细胞因子主导。在它们被单核细胞分泌之前，IL-1细胞因子被称为"炎性小体"的细胞内蛋白复合物加工，其可以感测细菌的挑战。本研究的目的是研究单核细胞中哪些炎性小体在A.伴放线菌使用D7SS菌株及其衍生的白细胞毒素和致死性膨胀毒素敲除突变株以1：10的细胞：细菌比例感染人单核细胞3 h。通过TaqMan定量实时聚合酶链反应（qPCR）研究细胞中各种炎性体组分的表达。NOD样受体蛋白（NLRP）1、NLRP 2和黑色素瘤中缺失（AIM）2炎性感受器及其效应物Caspase-1的表达不受影响。然而，NLRP 3上调，而NLRP 6下调。这种效果是不依赖于白细胞毒素或细胞致死膨胀毒素，所证明的使用特定的基因敲除突变株。IL-1 β和IL-18的表达也被细菌攻击上调。总之，A.伴随放线菌增强NLRP 3和降低NLRP 6炎性体表达，而不管其主要毒力因子，证实了该物种的高致病性特征，并为牙周炎症的机制提供了进一步的见解。(C)2012爱思唯尔有限公司保留所有权利。
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-1 beta 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. (C) 2012 Elsevier Ltd. All rights reserved.