Porphyromonas gingivalis cysteine proteinases in modulation of cell-mediated immune response in periodontitis

牙龈卟啉单胞菌半胱氨酸蛋白酶调节牙周炎细胞介导的免疫反应

• 批准号: nhmrc : 352479
• 负责人: Dr Lok Yun
• 金额: $ 15.2万
• 依托单位: The University of Sydney
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2005
• 资助国家: 澳大利亚
• 起止时间: 2005-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/porphyromonas-gingivalis-cysteine-response-periodontitis/98638
• 关键词: Porphyromonas; gingivalis; cysteine; proteinases; modulation

Chronic inflammatory diseases of the tissues supporting the teeth comprise some of the most widespread and common diseases to affect mankind. Recent research has indicated the major contributor to the most common form of destructive periodontal disease is the bacterium Porphyromonas gingivalis. This organism produces powerful enzymes which overcome the body's attempts to neutralise them. It is also known that the destructive phase of the disease is characterised by a change in the behaviour of the immune system cells which accumulate in the diseased tissues. This is manifest as a loss of protective immunity and replacement by ineffective or even tissue damaging responses. Critical in directing the pattern of behaviour of the immune system cells are the potent messenger molecules or cytokines which pass between cells. We have demonstrated that the bacterial proteinases can destroy a critical messenger molecule that instructs the defensive phagocytic cells to attack bacteria. These cells in return normally send a powerful signal back to the controlling T lymphocyte to amplify the protective signals. Associated bacterial molecules stimulate more secretion of messenger molecules which are paradoxically destroyed by the bacterial enzymes. This could cause chaos in the local tissue environment. Further, the bacterial proteinases can also eliminate some important surface molecules of T lymphocyte that are important in the activation process. The effect of this could produce impairment of T lymphocyte at periodontal sites. The planned research will define how the proteinases modulate T lymphocyte immune response. Further, the relation between the capacity of the bacterial enzymes to disrupt the vascular cells and the progression of periodontitis will also be determined.

牙齿支撑组织的慢性炎症性疾病是影响人类的最普遍和最常见的疾病之一。最近的研究表明，造成最常见的破坏性牙周病的主要原因是牙龈卟啉单胞菌。这种生物产生强大的酶，可以克服身体试图中和它们的努力。人们还知道，疾病的破坏阶段的特征是免疫系统细胞的行为改变，这些细胞在病变组织中积累。这表现为保护性免疫的丧失，取而代之的是无效甚至组织损伤的反应。在指导免疫系统细胞行为模式的关键是在细胞之间传递的有效的信使分子或细胞因子。我们已经证明，细菌蛋白酶可以破坏一个关键的信使分子，该分子指示防御性吞噬细胞攻击细菌。作为回报，这些细胞通常会向控制T淋巴细胞发送一个强大的信号，以放大保护信号。相关细菌分子刺激更多信使分子的分泌，而这些信使分子却被细菌酶破坏。这可能会导致局部组织环境混乱。此外，细菌蛋白酶还能消除T淋巴细胞活化过程中一些重要的表面分子。其作用可引起牙周部位T淋巴细胞损伤。计划中的研究将确定蛋白酶如何调节T淋巴细胞免疫反应。此外，细菌酶破坏血管细胞的能力与牙周炎进展之间的关系也将被确定。