Porphyromonas gingivalissuppresses adaptive immunity in periodontitis, atherosclerosis, and Alzheimer’s disease

Abstract

Porphyromonas gingivalis, a keystone pathogen in chronic periodontitis, has been found to associate with remote body organ inflammatory pathologies, including atherosclerosis and Alzheimer’s disease (AD). Although P. gingivalis has a plethora of virulence factors, much of its pathogenicity is surprisingly related to the overall immunosuppression of the host. This review focuses on P. gingivalis aiding suppression of the host’s adaptive immune system involving manipulation of cellular immunological responses, specifically T cells and B cells in periodontitis and related conditions. In periodontitis, this bacterium inhibits the synthesis of IL-2 and increases humoral responses. This reduces the inflammatory responses related to T- and B-cell activation, and subsequent IFN-γ secretion by a subset of T cells. The T cells further suppress upregulation of programmed cell death-1 (PD-1)-receptor on CD+cells and its ligand PD-L1 on CD11b+-subset of T cells. IL-2 downregulates genes regulated by immune response and induces a cytokine pattern in which the Th17 lineage is favored, thereby modulating the Th17/T-regulatory cell (Treg) imbalance. The suppression of IFN-γ-stimulated release of interferon-inducible protein-10 (IP-10) chemokine ligands [ITAC (CXCL11) and Mig (CXCL9)] by P. gingivalis capsular serotypes triggers distinct T cell responses and contributes to local immune evasion by release of its outer membrane vesicles. In atherosclerosis, P. gingivalis reduces Tregs, transforms growth factor beta-1 (TGFβ-1), and causes imbalance in the Th17 lineage of the Treg population. In AD, P. gingivalis may affect the blood–brain barrier permeability and inhibit local IFN-γ response by preventing entry of immune cells into the brain. The scarcity of adaptive immune cells in AD neuropathology implies P. gingivalis infection of the brain likely causing impaired clearance of insoluble amyloid and inducing immunosuppression. By the effective manipulation of the armory of adaptive immune suppression through a plethora of virulence factors, P. gingivalis may act as a keystone organism in periodontitis and in related systemic diseases and other remote body inflammatory pathologies.

Systemic inflammatory impact of periodontitis on cognitive impairment

“…Results should be quite different from serum biomarkers. In this study, findings from serum biomarkers may be attributable to an incapacity of patients with cognitive impairment to establish an adequate inflammatory response or to the short half‐life of the serum biomarkers analysed, which hampers evaluation of true levels after a period of inflammation or possibly by the well‐documented ability of P gingivalis (a keystone pathogen in chronic periodontitis) to suppress both the innate and adaptive immune responses . A high collinearity was also found among the inflammation biomarkers studied, which might have introduced a bias despite adjustments of the model.…”

Citrullination as a plausible link to periodontitis, rheumatoid arthritis, atherosclerosis and Alzheimer’s disease

“…Thus, P. gingivalis is a typical example of a pathogen that shows this trait by adapting to challenging inflammophilic environments of the host directed to kill it [8]. The virulence and potential pathogenic effects of P. gingivalis are diverse and, through them, this bacterium can affect many different organs and diseases [3,6,7,9,10]. The virulence factor under focus here is the enzyme P. gingivalis peptidyl-arginine deiminase (PPAD).…”

“…An underlying feature of stroke pathology includes vascular infections where P. gingivalis is often identified [53]. Increased evidence links peripheral infections with AD, and lipopolysaccharide (LPS) entry into the ageing brain generates cytokines via innate immune responses (Figure 3) [9]. LPS ischaemia from atherosclerosis and hypoxia link P. gingivalis with early death of erythrocytes for the supply of haem.…”

Oral Surgery in the Human Microbiota Era the role of Periodontal Bacteria

“…The incidence of bacteremia and related systemic diseases due to oral anaerobic bacteria following different procedures such as: endodontic treatment, tooth extraction, periodontal surgery, tongue scraping and root scaling has been well documented [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] and anaerobe periodontal bacteria are isolated more frequently than facultative anaerobic bacteria, such as Streptococcus spp. [28].…”