Abstract
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 [Ca2+]i, 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.
Highlights
Accumulating amount of data during recent years support an association between periodontitis and atherosclerosis, which both are inflammatory conditions involving different kinds of immune cells [1]
Regulatory T-cells and their release of the anti-inflammatory cytokine IL-10 have, in response to IL-2, been shown to exert anti-atherogenic effects [3,8,9]. Both CD4+ and CD8+ T-cells are present in atherosclerotic lesions [10], and may upon activation amplify the inflammatory condition in the atherosclerotic plaque through secretion of cytokines
Representative traces of the calcium changes following treatment of Jurkat T-cells with viable E. coli MG1655, viable P. gingivalis and heat-killed P. gingivalis are shown in figure 1b
Summary
Accumulating amount of data during recent years support an association between periodontitis and atherosclerosis, which both are inflammatory conditions involving different kinds of immune cells [1]. Regulatory T-cells and their release of the anti-inflammatory cytokine IL-10 have, in response to IL-2, been shown to exert anti-atherogenic effects [3,8,9]. Both CD4+ and CD8+ T-cells are present in atherosclerotic lesions [10], and may upon activation amplify the inflammatory condition in the atherosclerotic plaque through secretion of cytokines. Sasaki and colleagues [11] suggested the use of anti-CD3 to prevent atherosclerosis development and progression They showed that administration of anti-CD3 activated regulatory T-cells and reduced atherosclerotic lesions and accumulation of other immune cells. Unravelling the effects of the periodontal pathogen Porphyromonas gingivalis on T-cells will contribute to the clarification of the mechanisms applied by this pathogen to evade host immune responses and cause disease
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