Figure 5
Model of immune homeostasis disruption and dysbiosis by P. gingivalis. DC-SIGN - TLR2/CXCR4 crosstalk activated by ligation via P. gingivalis Mfa1 - FimA, respectively, activates STAT3, resulting in downstream AKT1 activation that phosphorylates and inactivates FOXO1. Direct suppression of apoptotic activity through BIM also occurs. DC-SIGN routes P. gingivalis into non-autophagosomal compartments where they survive. Upon phosphorylation by AKT1 the FOXO proteins are excluded from the nucleus and are sequestered or degraded. FOXO inactivation contributes to extended cell survival as FOXO members activate genes encoding pro-apoptotic molecules including Bcl-2-member BIM. The resultant MDDSCs are highly resistant to apoptosis and IDO-1 competent, traveling to local and distant sites bearing the bacteria and promoting immunosuppression through induced-Tregs (FOXP3). In addition to the immunosuppressive route through DC-SIGN by DPG3 (Mfa1), \FimA (MFI) leads the direct oncogenesis route through CXCR4.
