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Infect Immun, April 1998, p. 1660-1665, Vol. 66, No. 4
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Local Chemokine Paralysis, a Novel Pathogenic
Mechanism for Porphyromonas gingivalis
Richard P.
Darveau,1,2,*
Carol M.
Belton,3
Robert A.
Reife,1 and
Richard J.
Lamont3
Bristol-Myers Squibb Pharmaceutical Research
Institute, Seattle, Washington 98121,1 and
Departments of Periodontics2 and
Oral Biology,3 School of Dentistry,
University of Washington, Seattle, Washington 98195
Received 9 June 1997/Returned for modification 26 September
1997/Accepted 15 January 1998
Periodontitis, which is widespread in the adult population, is a
persistent bacterial infection associated with Porphyromonas gingivalis. Gingival 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 leukocytes, was secreted by
gingival epithelial cells in response to components of the normal oral flora. In contrast, P. gingivalis was found to strongly
inhibit IL-8 accumulation from gingival epithelial cells.
Inhibition was associated with a decrease in mRNA for IL-8. Antagonism
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 unable to
antagonize IL-8 accumulation. Invasion-dependent destruction of the
gingival IL-8 chemokine gradient at sites of P. gingivalis
colonization (local chemokine paralysis) will severely impair mucosal defense and represents a novel mechanism for
bacterial colonization of host tissue.
*
Corresponding author. Mailing address: Department of
Periodontics, University of Washington School of Dentistry, Seattle, WA
98195. Phone: (206) 543-9514. Fax: (206) 616-7478. E-mail: rdarveau{at}u.washington.edu.
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