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Analysis of Mechanism for Specific Immune Response Induction to Periodontopathic Bacteria

牙周病菌特异性免疫反应诱导机制分析

基本信息

批准号：
12470469
负责人：
SHIMAUCHI Hidetoshi
金额：
$ 8.13万
依托单位：
TOHOKU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470469/
关键词：
Dendritic Cells Porphyromonas gingivalis LPS Fimbriae CD14 CD16 CD40 P. ginigivalis 認識機構炎症性サイトカイン産生

项目摘要

Primary immune responses are initiated by dendritic cells (DC), which inform naive Th cells about invading pathogens. DC settle as interstitial DC and Langerhans cells in peripheral non-lymphoid tissues including gingiva. These peripheral DC capture and process Ag at the site of inflammation, and then migrate to lymph nodes to prime Th cells. DC undergo a series of events leading to irreversible maturation upon stimulation with invading bacteria, and up-regulate cytokine production and surface molecule expression with different kinetics. To investigate the responses DC during periodontal infection, we analyzed(1)the sensitivitly to Human Leukocyte Elastase (HLE) digestion of CD40 on DC,(2)the effects of LPS and fimbriae from P. gingivalis on the phenotype of human in DC. CD40 on DC was resistant to HLE treatment, unlike the molecule of human gingival fibroblasts, suggesting that DC were capale to stimulate the local immune responses after PMNL infiltration. Furthermore, P. gingivalis L … More PS and fimbriae preferentially up-regulated CD14 and CD16 expression on immature PBDC (CD14^-CD16^-), although E. coli LPS did not alter the expression of these molecules. P. gingivalis LPS-induced CD14^+CD16^+ cells strongly expressed dendritic cell markers: Cdla and HLA-DR, and CD54 was highly expressed. However, CD40, CD80, CD83, CD86 expression was lower than E.coli LPS-stimulated DC, suggesting these cells were in DC with weak immunnostimulatory activity. P.gingivalis LPS was a weaker stimulator in terms of IL-6, IL-8, IL-10, IL-12, and RANTES production from DC as compared to E.coli LPS. Both LPS stimulated-DC induced comparable up-take of dextran-FITC, although P.gingivalis induced the statistically weaker allogenic T cell proliferation. These results suggestively indicated P. gingivalis LPS and fimbriae trigger a maturation of DC with unique characteristics, that modulate immune responses occurred at the site of periodontal infection. P.gingivalis-induced CD14^+CD16^+DC subsets may contribute to induction of chronic inflammation. Less

初级免疫反应是由树突状细胞（DC）发起的，它将病原体入侵的信息告知幼稚的Th细胞。DC以间质DC和朗格汉斯细胞的形式存在于包括牙龈在内的周围非淋巴组织中。这些外周DC在炎症部位捕获和处理Ag，然后迁移到淋巴结到初始Th细胞。DC在入侵细菌的刺激下发生一系列不可逆成熟的事件，并以不同的动力学上调细胞因子的产生和表面分子的表达。为了研究牙周感染对DC的反应，我们分析了(1)DC对人白细胞弹性酶（HLE）消化CD40的敏感性，(2)LPS和牙龈卟啉卟啉菌菌毛对DC人表型的影响。与人牙龈成纤维细胞分子不同，DC上的CD40对HLE治疗具有耐药性，这表明DC能够刺激PMNL浸润后的局部免疫反应。此外，P. gingivalis L . More PS和菌毛优先上调未成熟PBDC上CD14和CD16的表达（CD14^-CD16^-），尽管大肠杆菌LPS没有改变这些分子的表达。P. gingivalis lps诱导CD14^+CD16^+细胞强烈表达树突状细胞标志物：Cdla和HLA-DR， CD54高表达。然而，CD40、CD80、CD83、CD86的表达低于大肠杆菌lps刺激的DC，表明这些细胞处于DC中，免疫刺激活性较弱。与大肠杆菌LPS相比，P.gingivalis LPS在DC产生IL-6、IL-8、IL-10、IL-12和RANTES方面的刺激作用较弱。两种LPS刺激的dc诱导了相当的葡聚糖- fitc摄取，尽管P.gingivalis诱导的同种异体T细胞增殖在统计学上较弱。这些结果提示牙龈假单胞菌脂多糖和菌毛触发DC成熟具有独特的特征，调节发生在牙周感染部位的免疫反应。牙龈卟啉菌诱导的CD14^+CD16^+DC亚群可能有助于诱导慢性炎症。少