Division of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
PLoS One. 2012;7(9):e45192. doi: 10.1371/journal.pone.0045192. Epub 2012 Sep 12.
Several studies support an association between the chronic inflammatory diseases periodontitis and atherosclerosis with a crucial role for the periodontal pathogen Porphyromonas gingivalis. However, the interplay between this pathogen and the adaptive immune system, including T-cells, is sparsely investigated. Here we used Jurkat T-cells to determine the effects of P. gingivalis on T-cell-mediated adaptive immune responses. We show that viable P. gingivalis targets IL-2 expression at the protein level. Initial cellular events, including ROS production and Ca(2+), were elevated in response to P. gingivalis, but AP-1 and NF-κB activity dropped below basal levels and T-cells were unable to sustain stable IL-2 accumulation. IL-2 was partially restored by Leupeptin, but not by Cathepsin B Inhibitor, indicating an involvement of Rgp proteinases in the suppression of IL-2 accumulation. This was further confirmed by purified Rgp that caused a dose-dependent decrease in IL-2 levels. These results provide new insights of how this periodontal pathogen evades the host adaptive immune system by inhibiting IL-2 accumulation and thus attenuating T-cell proliferation and cellular communication.
几项研究支持慢性炎症性疾病牙周炎和动脉粥样硬化与牙周病原体牙龈卟啉单胞菌之间存在关联，该病原体在其中起着关键作用。然而，这种病原体与适应性免疫系统（包括 T 细胞）之间的相互作用研究甚少。在这里，我们使用 Jurkat T 细胞来确定牙龈卟啉单胞菌对 T 细胞介导的适应性免疫反应的影响。我们表明，活的牙龈卟啉单胞菌靶向 IL-2 的蛋白水平表达。响应牙龈卟啉单胞菌，初始细胞事件（包括 ROS 产生和 Ca(2+)）升高，但 AP-1 和 NF-κB 活性降至基础水平以下，T 细胞无法维持稳定的 IL-2 积累。Leupeptin 部分恢复了 IL-2，但 Cathepsin B Inhibitor 没有，表明 Rgp 蛋白酶参与了 IL-2 积累的抑制。这进一步通过纯化的 Rgp 得到证实，Rgp 导致 IL-2 水平呈剂量依赖性下降。这些结果提供了新的见解，即这种牙周病原体如何通过抑制 IL-2 积累从而减弱 T 细胞增殖和细胞通讯来逃避宿主适应性免疫系统。
