Impaired immune tolerance to Porphyromonas gingivalis lipopolysaccharide promotes neutrophil migration and decreased apoptosis

Svetislav Zaric, Charles Shelburne, Richard Darveau, Derek J Quinn, Sinéad Weldon, Clifford C Taggart, Wilson A Coulter

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)


Periodontitis, a chronic inflammatory disease of the tissues supporting the teeth, is characterized by an exaggerated host immune and inflammatory response to periopathogenic bacteria. Toll-like receptor activation, cytokine network induction, and accumulation of neutrophils at the site of inflammation are important in the host defense against infection. At the same time, induction of immune tolerance and the clearance of neutrophils from the site of infection are essential in the control of the immune response, resolution of inflammation, and prevention of tissue destruction. Using a human monocytic cell line, we demonstrate that Porphyromonas gingivalis lipopolysaccharide (LPS), which is a major etiological factor in periodontal disease, induces only partial immune tolerance, with continued high production of interleukin-8 (IL-8) but diminished secretion of tumor necrosis factor alpha (TNF-a) after repeated challenge. This cytokine response has functional consequences for other immune cells involved in the response to infection. Primary human neutrophils incubated with P. gingivalis LPS-treated naïve monocyte supernatant displayed a high migration index and increased apoptosis. In contrast, neutrophils treated with P. gingivalis LPS-tolerized monocyte supernatant showed a high migration index but significantly decreased apoptosis. Overall, these findings suggest that induction of an imbalanced immune tolerance in monocytes by P. gingivalis LPS, which favors continued secretion of IL-8 but decreased TNF-a production, may be associated with enhanced migration of neutrophils to the site of infection but also with decreased apoptosis and may play a role in the chronic inflammatory state seen in periodontal disease.
Original languageEnglish
Pages (from-to)4151-4156
Number of pages6
JournalInfection and Immunity
Issue number10
Early online date2 Aug 2010
Publication statusPublished - Oct 2010


  • apoptosis
  • caspase 3
  • cell Line
  • cell movement
  • gene expression regulation
  • humans
  • immune tolerance
  • interleukin-8
  • lipopolysaccharides
  • membrane potential, mitochondrial
  • neutrophils
  • Porphyromonas gingivalis
  • tumor necrosis factor-alpha


Dive into the research topics of 'Impaired immune tolerance to Porphyromonas gingivalis lipopolysaccharide promotes neutrophil migration and decreased apoptosis'. Together they form a unique fingerprint.

Cite this