Porphyromonas gingivalis lipopolysaccharide is poorly recognized by molecular components of innate host defense in a mouse model of early inflammation

Abstract

Porphyromonas gingivalis is a gram-negative bacterium that is associated with periodontitis. It has been hypothesized that destruction of bone and periodontal connective tissue is associated with colonization of the subgingival crevicular space by P. gingivalis, although how these bacteria overcome innate host defenses is largely unknown. To examine the early cellular and molecular events of P. gingivalis interaction with host tissues, we compared lipopolysaccharide (LPS) isolated from this bacterium with Escherichia coli LPS, a potent inflammatory mediator, in a mouse model of acute inflammation. In these studies, mice were given intramuscular injections of either P. gingivalis LPS or E. coli LPS and then sacrificed after 4 h. Reverse transcriptase-PCR analysis showed that expression of mRNAs for E-and P-selectins was higher in E. coli LPS-injected muscles than in P. gingivalis LPS-injected or control phosphate-buffered-saline-injected muscles. Similarly, monocyte chemotactic protein 1 and fibroblast-induced cytokine mRNAs were expressed in E. coli LPS-injected muscles whereas their expression was reduced or absent in P. gingivalis LPS-injected samples. These results were confirmed by in situ hybridization whereby stronger hybridization for selectin mRNAs was observed in the endothelium of capillaries from E. coli LPS-injected samples than in that from P. gingivalis LPS-injected muscles. In addition, many monocytes expressing monocyte chemotactic protein 1 mRNA and polymorphonuclear leukocytes expressing fibroblast-induced cytokine mRNA were observed in E. coli LPS-injected muscles whereas only a few cells were identified in P. gingivalis LPS-injected muscles. These results demonstrate that compared with E. coli, P. gingivalis has a low biologically reactive LPS as measured by its weak activation of inflammation. This may allow P. gingivalis to evade innate host defense mechanisms, resulting in colonization and chronic disease.

Role of bacteria in health and disease of periodontal tissues

“…In keeping with the proposed hypothesis of P. gingivalis stealth-like activities, its lipopolysaccharide is a poor inducer of inflammatory mediators in epithelial and endothelial cells and antagonizes their expression by lipopolysaccharide from other bacteria (28,36,191). However, and much like responses with P. gingivalis fimbriae, P. gingivalis lipopolysaccharide promotes the expression of proinflammatory cytokines and chemokines in monocytes ⁄ macrophages (265).…”

Granulocyte elastase activity in static and flow gingival crevicular fluid

“…Different organisms play different rô les in the disease process and P. gingivalis seems to be different from other gram-negative bacteria in its capacity to stimulate and activate the innate host inflammatory response (Darveau et al 1997). Recent studies showed that P. gingivalis plays an important rô le in suppressing the innate host inflammatory response by various mechanisms , Reife et al 1995, Cunningham et al 1996. P. gingivalis inhibits the ability of leukocytes to bind to endothelial cells and migrate into the extravascular compartment, and therefore blocks a key step in the inflammatory response (Darveau et al 1997).…”

Cyclooxygenase‐2‐Dependent Prostaglandin Production by Peripheral Blood Monocytes Stimulated With Lipopolysaccharides Isolated From Periodontopathogenic Bacteria

“…P. gingivalis has been reported to have a biologically low reactive LPS. 41,42 The reason for this differential activation may be due to the difference in the structure of LPS molecules or the difference in their receptors on the cells. It has been shown that P. gingivalis-LPS extracted by the phenol-water method does not contain heptose and 2keto position of P. gingivalis-LPS differs from that of E. coli-LPS.…”