Porphyromonas gingivalis suppresses adaptive immunity in periodontitis, atherosclerosis, and alzheimer's disease

Abstract

Porphyromonas gingivalis, a keystone pathogen in chronic periodontitis, has been found to associate withremote 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 tothe overall immunosuppression of the host. This review focuses on P. gingivalis aiding suppression of the host'sadaptive immune system involving manipulation of cellular immunological responses, specifically Tcells and Bcells in periodontitis and related conditions. In periodontitis, this bacterium inhibits the synthesis of IL-2 andincreases humoral responses. This reduces the inflammatory responses related to T- and B-cell activation, andsubsequent IFN-γ secretion by a subset of Tcells. The Tcells further suppress upregulation of programmed celldeath-1 (PD-1)-receptor on CD+cells and its ligand PD-L1 on CD11b+-subset of T cells. IL-2 downregulatesgenes 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 releaseof interferon-inducible protein-10 (IP-10) chemokine ligands [ITAC (CXCL11) and Mig (CXCL9)] byP. gingivalis capsular serotypes triggers distinct T cell responses and contributes to local immune evasion byrelease of its outer membrane vesicles. In atherosclerosis, P. gingivalis reduces Tregs, transforms growth factorbeta-1 (TGFβ-1), and causes imbalance in the Th17 lineage of the Treg population. In AD, P. gingivalis mayaffect the blood-brain barrier permeability and inhibit local IFN-γ response by preventing entry of immunecells into the brain. The scarcity of adaptive immune cells in AD neuropathology implies P. gingivalis infectionof the brain likely causing impaired clearance of insoluble amyloid and inducing immunosuppression. By theeffective 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 remotebody inflammatory pathologies.