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

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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