LOCAL CHEMOKINE PARALYSIS, A NOVEL PATHOGENIC MECHANISM FOR PORPHYROMONAS-GINGIVALIS

Periodontitis, which is widespread in the adult population, is a persi stent bacterial infection associated with Porphyromonas gingivalis. Gi ngival epithelial cells are among the first cells encountered by both P. gingivalis and commensal oral bacteria. The chemokine interleukin 8 (IL-8), a potent chemoattractant and activator of polymorphonuclear l eukocytes, was secreted by gingival epithelial cells in response to co mponents of the normal oral flora. In contrast, P. gingivalis was foun d to strongly inhibit IL-8 accumulation from gingival epithelial cells . Inhibition was associated with a decrease in mRNA for IL-8. Antagoni sm of IL-8 accumulation did not occur in KB cells, an epithelial cell line that does not support high levels of intracellular invasion by P. gingivalis. Furthermore, a noninvasive mutant of P. gingivalis was un able to antagonize IL-8 accumulation. Invasion-dependent destruction o f the gingival IL-8 chemokine gradient at sites of P. gingivalis colon ization (local chemokine paralysis) will severely impair mucosal defen se and represents a novel mechanism for bacterial colonization of host tissue.