title: Suppression of T-cell chemokines by Porphyromonas gingivalis.
abstract: Porphyromonas gingivalis is a major pathogen in periodontal disease and is associated with immune dysbiosis. In this study, we found that P. gingivalis did not induce the expression of the T-cell chemokine IP-10 (CXCL10) from neutrophils, peripheral blood mononuclear cells (PBMCs), or gingival epithelial cells. Furthermore, P. gingivalis suppressed gamma interferon (IFN-γ)-stimulated release of IP-10, ITAC (CXCL11), and Mig (CXCL9) from epithelial cells and inhibited IP-10 secretion in a mixed infection with the otherwise stimulatory Fusobacterium nucleatum. Inhibition of chemokine expression occurred at the level of gene transcription and was associated with downregulation of interferon regulatory factor 1 (IRF-1) and decreased levels of Stat1. Ectopic expression of IRF-1 in epithelial cells relieved P. gingivalis-induced inhibition of IP-10 release. Direct contact between P. gingivalis and epithelial cells was not required for IP-10 inhibition. These results highlight the immune-disruptive potential of P. gingivalis. Suppression of IP-10 and other Th1-biasing chemokines by P. gingivalis may perturb the balance of protective and destructive immunity in the periodontal tissues and facilitate the pathogenicity of oral microbial communities.
authors.affiliation: Center for Oral Health and Systemic Disease, School of Dentistry, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Jauregui
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Wright
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Silvia M
authors.initials: SM
authors.lastname: Uriarte
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Lamont
mesh_terms: D016866:Bacteroidaceae Infections / Q000276:immunology / Q000382:microbiology; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000235:genetics / Q000276:immunology*; D054371:Chemokine CXCL11 / Q000235:genetics / Q000276:immunology; D054370:Chemokine CXCL9 / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology; D005674:Fusobacterium Infections / Q000276:immunology / Q000382:microbiology; D016967:Fusobacterium nucleatum / Q000276:immunology; D005881:Gingiva / Q000166:cytology; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D016966:Porphyromonas gingivalis / Q000276:immunology*; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000382:microbiology*; D014158:Transcription, Genetic
chemical_list: C114753:CXCL10 protein, human; C515202:CXCL11 protein, human; C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D007371:Interferon-gamma