title: Altered T-cell responses by the periodontal pathogen Porphyromonas gingivalis.
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 [Ca(2+)](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.
authors.affiliation: Division of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden. hazem.khalaf@oru.se
authors.forename: Hazem
authors.initials: H
authors.lastname: Khalaf
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Bengtsson
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism; D002118:Calcium / Q000276:immunology / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000276:immunology; D000080867:Gingipain Cysteine Endopeptidases; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019169:Jurkat Cells; D007976:Leupeptins / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016966:Porphyromonas gingivalis / Q000201:enzymology / Q000276:immunology* / Q000502:physiology; D059748:Proteolysis / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D018829:Adhesins, Bacterial; D015853:Cysteine Proteinase Inhibitors; D000080867:Gingipain Cysteine Endopeptidases; D007376:Interleukin-2; D007976:Leupeptins; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; D008156:Luciferases; D003546:Cysteine Endopeptidases; C032854:leupeptin; D002118:Calcium