Porphyromonas gingivalis-Host Interactions: Open War or Intelligent Guerilla Tactics?

P. gingivalis is predominantly recognized by the TLR2/1 heterodimer []. Through its fimbriae, the pathogen binds CXCR4 which cross-talks with and suppresses the TLR2/1-induced TIRAP/MyD88-mediated antimicrobial pathway []. The mechanism involves CXCR4-induced activation of cAMP-dependent protein kinase A (PKA) which suppresses NF-κB activation and induction of proinflammatory cytokines and antimicrobial molecules, such as the inducible nitric oxide synthase (iNOS). These inhibitory effects promote P. gingivalis survival in vitro and in vivo []. The CXCR4 mechanism does not however inhibit the P. gingivalis-induced inside-out signaling, which proceeds via phosphatidylinositol 3-kinase (PI3K) and cytohesin-1 and activates the high-affinity conformation of CR3 [, ](and unpublished data). Intriguingly, P. gingivalis interacts with activated CR3 and is thereby internalized; this is a relatively safe portal of entry since CR3 is not linked to vigorous microbicidal mechanisms [, ]. Moreover, the P. gingivalis-CR3 interaction induces outside-in signaling, which via extracellular signal-related kinase 1/2 (ERK1/2) downregulates IL-12 p35 and p40 mRNA expression [], possibly through ERK1/2 suppression of IRF-1 and ICSBP transcription factors []. At the protein level, the outcome is reduced production of bioactive IL-12 resulting in impaired immune clearance of P. gingivalis in vivo [].

Publication

Porphyromonas gingivalis-Host Interactions: Open War or Intelligent Guerilla Tactics?. () George Hajishengallis. Microbes Infect. ;11(6-7):637-645. Figure: F1. All organisms Homo sapiens Danio rerio

Disease mentions