Integrin activation by bacterial fimbriae through a pathway involving CD14, Toll-like receptor 2, and phosphatidylinositol-3-kinase

Eur J Immunol. 2005 Apr;35(4):1201-10. doi: 10.1002/eji.200425883.


CD11b-CD18 and other integrins play important roles in immunity and inflammation and require prior activation through inside-out signaling to efficiently bind their ligands. We present evidence for a novel TLR2-dependent signaling pathway that leads to CD11b-CD18 activation in human monocytes or neutrophils upon recognition of Porphyromonas gingivalis fimbriae through CD14. The activated binding-state of CD11b-CD18, which involves induction of conformational changes, was monitored through detection of an activation-specific epitope of CD11b. The ability of fimbriae to induce this activation epitope was significantly inhibited by a mAb to TLR2, but not to TLR4 or unrelated surface molecules. Moreover, the ability of fimbriae to activate CD11b-CD18 was significantly inhibited by pharmacological inhibitors of phosphatidylinositol-3-kinase but not of PKC or of p38 mitogen-activated protein kinase. The signaling pathway activated by fimbriae is distinct from that which is activated by N-formyl-Met-Leu-Phe, a prototypical integrin activator, since the former was insensitive to pertussis toxin. This novel function of TLR2 as a signaling receptor for pathogen-induced activation of CD11b-CD18 may play a significant role in infection-driven chronic inflammatory conditions, such as periodontal disease or atherosclerosis, where P. gingivalis has been implicated.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • CD11b Antigen / metabolism
  • CD18 Antigens / metabolism
  • Fimbriae, Bacterial / metabolism*
  • Humans
  • Integrins / metabolism*
  • Lipopolysaccharide Receptors / immunology
  • Lipopolysaccharide Receptors / metabolism*
  • Membrane Glycoproteins / metabolism*
  • Neutrophils / metabolism
  • Neutrophils / microbiology
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphotransferases / metabolism
  • Porphyromonas gingivalis / metabolism*
  • Receptors, Cell Surface / metabolism*
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptors


  • CD11b Antigen
  • CD18 Antigens
  • Integrins
  • Lipopolysaccharide Receptors
  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • TLR2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Phosphotransferases
  • Phosphatidylinositol 3-Kinases