Table 1.
Potential mechanisms of human periodontal bacterial involvement in extra-oral pathologies
| Bacterium | Effector molecule | Target | Outcome | Refs |
|---|---|---|---|---|
| Porphyromonas gingivalis | Gingipains | PECAM1, VE-cadherin, in vascular endothelial cells | Impairment of endothelial junctional integrity, vascular damage | 15 |
| Gingipains | Tau protein, APOE in the brain | Alterations promoting neurotoxic/inflammatory effects | 11 | |
| PPAD | Proteins, including host molecules, such as fibrinogen and α-enolase | Citrullination of protein autoantigens leading to ACPA induction | 125–127 | |
| Mfa1 fimbrial protein | DC-SIGN on DCs | Hijacking the trafficking of DCs; enhanced atherogenic and anti-apoptotic potential | 13,84 | |
| BCAT | Respective α-keto acidsa | Increased plasma levels of BCAAs (Leu, Ile and Val); insulin resistance | 52 | |
| Aggregatibacter actinomycetemcomitans | Leukotoxin A | β2 Integrin on neutrophils | PAD hyperactivation and release of citrullinated autoantigens through cytolysis, leading to ACPA induction | 12 |
| Klebsiella pneumoniae | Unspecified TLR agonists | TLRs on colonic epithelial cells and DCs | IL-18 secretion, TH1 cell expansion and gut inflammation | 8 |
| Fusobacterium nucleatum | Fap2 | Gal-GalNac on CRC cells | CRC targeting and enrichment; induction of pro-metastatic chemokines | 7,113 |
| Fap2 | TIGIT on T cells and NK cells | Tumour immune evasion | 10 | |
| FadA | E-cadherin on CRC cells | Activation of Wnt–β-catenin signalling and CRC cell proliferation | 112,118 |
ACPA, anti-citrullinated protein antibody; APOE, apolipoprotein E; BCAA, branched-chain amino acid; BCAT, branched-chain amino acid aminotransferase; CRC, colorectal cancer; DC, dendritic cell; DC-SIGN, DC-specific ICAM3-grabbing non-integrin; NK, natural killer; PAD, peptidyl-arginine deiminase; PECAM1, platelet endothelial cell adhesion molecule; PPAD, Porphyromonas gingivalis peptidyl-arginine deiminase; TH1 cell, T helper 1 cell; TIGIT, T cell immunoreceptor with immunoglobulin and ITIM domains; TLR, Toll-like receptor; VE-cadherin, vascular endothelial cadherin. aα-ketoisocaproate (Leu), α-keto-β-methylvalerate (Ile) and α-ketoisovalerate (Val).