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Monocytic cell activation by Nonendotoxic glycoprotein from Prevotella intermedia ATCC 25611 is mediated by toll-like

S Sugawara1, S Yang, K Iki

  • 1Department of Microbiology and Immunology, Tohoku University School of Dentistry, Sendai 980-8575, Japan. sugawars@mail.cc.tohoku.ac.jp

Infection and Immunity
|July 12, 2001
PubMed

Insights

Prevotella glycoprotein (PGP) activates monocytic cells via Toll-like receptor 2 (TLR2) and CD14, independent of lipopolysaccharide (LPS). This non-LPS molecule offers new insights into immune cell activation by oral bacteria.

Area of Science:

  • Immunology
  • Microbiology
  • Biochemistry

Background:

  • Lipopolysaccharide (LPS) from certain bacteria activates immune cells, but the exact components responsible are debated.
  • Porphyromonas gingivalis and Prevotella intermedia LPS activate non-LPS-responsive mouse cells, suggesting alternative activators.

Purpose of the Study:

  • To identify and characterize a non-LPS bioactive component from Prevotella intermedia.
  • To elucidate the mechanism of action of this component on monocytic cells.

Main Methods:

  • Purification of Prevotella glycoprotein (PGP) from P. intermedia.
  • Treatment of human monocytic THP-1 cells and murine macrophages with PGP.
  • Analysis of cell surface marker expression (CD14, TLR2, TLR4) and cytokine production (interleukin-8).
  • Use of TLR2-deficient macrophages and inhibition assays with antibodies and lipid A precursor.

Main Results:

  • A non-endotoxic glycoprotein (PGP) was purified from P. intermedia.
  • PGP induced interleukin-8 production in mature THP-1 cells, comparable to Salmonella LPS.
  • PGP-induced activation was dependent on CD14 and Toll-like receptor 2 (TLR2), but not TLR4.
  • PGP activity required LPS-binding protein and was inhibited by a lipid A precursor.

Conclusions:

  • Prevotella glycoprotein (PGP) activates monocytic cells through a CD14- and TLR2-dependent pathway.
  • This activation mechanism is distinct from typical LPS-mediated signaling.
  • PGP represents a novel immune-activating molecule from oral bacteria.

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