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

支持牙齿的组织的慢性炎性疾病包括影响人类的一些最广泛和最常见的疾病。最近的研究表明，最常见的破坏性牙周病的主要贡献者是细菌牙龈卟啉单胞菌。这种有机体产生强大的酶，克服身体试图中和它们。还已知疾病的破坏性阶段的特征在于在患病组织中积累的免疫系统细胞的行为的变化。这表现为保护性免疫力的丧失和无效或甚至组织损伤反应的替代。在指导免疫系统细胞的行为模式中至关重要的是在细胞之间传递的有效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，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淋巴细胞发送强大的信号，以放大保护信号。相关的细菌分子刺激更多的信使分子分泌，而这些信使分子却被细菌酶破坏。这可能导致局部组织环境混乱。此外，细菌蛋白酶还可以清除T淋巴细胞表面的一些重要分子，这些分子在活化过程中起重要作用。这一作用可能导致牙周组织中T淋巴细胞的损伤。计划中的研究将确定蛋白酶如何调节T淋巴细胞免疫应答。此外，还将确定细菌酶破坏血管细胞的能力与牙周炎进展之间的关系。

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.