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Updated: May 15, 2026

Porphyromonas gingivalis as a Model Organism for Assessing Interaction of Anaerobic Bacteria with Host Cells
Published on: December 17, 2015
Mechanism and implications of CXCR4-mediated integrin activation by Porphyromonas gingivalis
G Hajishengallis1, M L McIntosh, S-I Nishiyama
1Department of Microbiology, University of Pennsylvania School of Dental Medicine, Philadelphia, PA 19104, USA. geoh@dental.upenn.edu
Abstract:
In monocytes and macrophages, the interaction of Porphyromonas gingivalis with Toll-like receptor 2 (TLR2) leads to the activation of a MyD88-dependent antimicrobial pathway and a phosphatidylinositol-3 kinase (PI3K) -dependent pro-adhesive pathway, which activates the β2 -integrin complement receptor 3 (CR3). By means of its fimbriae, P. gingivalis binds CXC-chemokine receptor 4 (CXCR4) and induces crosstalk with TLR2 that inhibits the MyD88-dependent antimicrobial pathway. In this paper, we investigated the impact of the P. gingivalis-CXCR4 interaction on the pro-adhesive pathway. Using human monocytes, mouse macrophages, or receptor-transfected cell lines, we showed that the binding of P. gingivalis fimbriae to CXCR4 induces CR3 activation via PI3K, albeit in a TLR2-independent manner. An isogenic strain of P. gingivalis expressing mutant fimbriae that do not interact with CXCR4 failed to efficiently activate CR3, leading to enhanced susceptibility to killing in vivo compared with the wild-type organism. This in vivo observation is consistent with previous findings that activated CR3 mediates safe entry of P. gingivalis into macrophages. Taken together with our previous work, these results indicate that the interaction of P. gingivalis with CXCR4 leads to inhibition of antimicrobial responses and enhancement of pro-adhesive responses, thereby maximizing its adaptive fitness in the mammalian host.
Insights
Porphyromonas gingivalis binding to CXCR4 enhances its pro-adhesive pathway via PI3K, promoting bacterial entry into macrophages. This interaction inhibits antimicrobial responses, aiding bacterial survival in the host.
Area of Science:
- Microbiology
- Immunology
- Cell Biology
Background:
- Porphyromonas gingivalis interacts with Toll-like receptor 2 (TLR2) in monocytes and macrophages, activating antimicrobial and pro-adhesive pathways.
- P. gingivalis fimbriae bind CXC-chemokine receptor 4 (CXCR4), inhibiting antimicrobial pathways through crosstalk with TLR2.
Purpose of the Study:
- To investigate the impact of P. gingivalis-CXCR4 interaction on the pro-adhesive pathway.
- To understand how CXCR4 binding influences CR3 activation and bacterial survival.
Main Methods:
- Utilized human monocytes, mouse macrophages, and receptor-transfected cell lines.
- Examined the role of P. gingivalis fimbriae, PI3K, and TLR2 in CR3 activation.
- Compared the in vivo survival of wild-type P. gingivalis with an isogenic strain expressing mutant fimbriae.
Main Results:
- P. gingivalis fimbriae binding to CXCR4 activates CR3 via PI3K independently of TLR2.
- Mutant fimbriae unable to interact with CXCR4 resulted in inefficient CR3 activation and increased susceptibility to killing in vivo.
- Activated CR3 facilitates P. gingivalis entry into macrophages.
Conclusions:
- P. gingivalis interaction with CXCR4 inhibits antimicrobial responses and enhances pro-adhesive responses.
- This dual effect maximizes the bacterium's adaptive fitness and survival within the mammalian host.
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