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. 1997 Oct;65(10):3983–3990. doi: 10.1128/iai.65.10.3983-3990.1997

Porphyromonas gingivalis infection of oral epithelium inhibits neutrophil transepithelial migration.

P N Madianos 1, P N Papapanou 1, J Sandros 1
PMCID: PMC175572  PMID: 9316996

Abstract

Periodontal diseases are inflammatory disorders caused by microorganisms of dental plaque that colonize the gingival sulcus and, subsequently, the periodontal pocket. As in other mucosal infections, the host response to plaque bacteria is characterized by an influx of polymorphonuclear leukocytes (PMNs) to the gingival crevice. Neutrophil migration through the epithelial lining of the gingival pocket is thought to be the first line of defense against plaque bacteria. In order to model this phenomenon in vitro, we used the oral epithelial cell line KB and human PMNs in the Transwell system and examined the impact of Porphyromonas gingivalis-epithelial cell interactions on subsequent PMN transepithelial migration. We demonstrate here that P. gingivalis infection of oral epithelial cells failed to trigger transmigration of PMNs. Furthermore, it significantly inhibited neutrophil transmigration actively induced by stimuli such as N-formylmethionyl leucyl phenylalanine, interleukin-8 (IL-8), and the intestinal pathogen enterotoxigenic Escherichia coli. The ability of P. gingivalis to block PMN transmigration was strongly positively correlated with the ability to adhere to and invade epithelial cells. In addition, P. gingivalis attenuated the production of IL-8 and the expression of intercellular adhesion molecule 1 by epithelial cells. The ability of P. gingivalis to block neutrophil migration across an intact epithelial barrier may critically impair the potential of the host to confront the bacterial challenge and thus may play an important role in the pathogenesis of periodontal disease.

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Selected References

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  1. Agace W. W., Hedges S. R., Ceska M., Svanborg C. Interleukin-8 and the neutrophil response to mucosal gram-negative infection. J Clin Invest. 1993 Aug;92(2):780–785. doi: 10.1172/JCI116650. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Agace W. W., Patarroyo M., Svensson M., Carlemalm E., Svanborg C. Escherichia coli induces transuroepithelial neutrophil migration by an intercellular adhesion molecule-1-dependent mechanism. Infect Immun. 1995 Oct;63(10):4054–4062. doi: 10.1128/iai.63.10.4054-4062.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Agace W. W. The role of the epithelial cell in Escherichia coli induced neutrophil migration into the urinary tract. Eur Respir J. 1996 Aug;9(8):1713–1728. doi: 10.1183/09031936.96.09081713. [DOI] [PubMed] [Google Scholar]
  4. Agace W., Hedges S., Andersson U., Andersson J., Ceska M., Svanborg C. Selective cytokine production by epithelial cells following exposure to Escherichia coli. Infect Immun. 1993 Feb;61(2):602–609. doi: 10.1128/iai.61.2.602-609.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Attström R., Egelberg J. Emigration of blood neutrophils and monocytes into the gingival crevices. J Periodontal Res. 1970;5(1):48–55. doi: 10.1111/j.1600-0765.1970.tb01837.x. [DOI] [PubMed] [Google Scholar]
  6. Colgan S. P., Parkos C. A., Delp C., Arnaout M. A., Madara J. L. Neutrophil migration across cultured intestinal epithelial monolayers is modulated by epithelial exposure to IFN-gamma in a highly polarized fashion. J Cell Biol. 1993 Feb;120(3):785–798. doi: 10.1083/jcb.120.3.785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Consensus report. Periodontal diseases: pathogenesis and microbial factors. Ann Periodontol. 1996 Nov;1(1):926–932. doi: 10.1902/annals.1996.1.1.926. [DOI] [PubMed] [Google Scholar]
  8. Crowe S. E., Alvarez L., Dytoc M., Hunt R. H., Muller M., Sherman P., Patel J., Jin Y., Ernst P. B. Expression of interleukin 8 and CD54 by human gastric epithelium after Helicobacter pylori infection in vitro. Gastroenterology. 1995 Jan;108(1):65–74. doi: 10.1016/0016-5085(95)90009-8. [DOI] [PubMed] [Google Scholar]
  9. Cutler C. W., Kalmar J. R., Genco C. A. Pathogenic strategies of the oral anaerobe, Porphyromonas gingivalis. Trends Microbiol. 1995 Feb;3(2):45–51. doi: 10.1016/s0966-842x(00)88874-5. [DOI] [PubMed] [Google Scholar]
  10. Duncan M. J., Nakao S., Skobe Z., Xie H. Interactions of Porphyromonas gingivalis with epithelial cells. Infect Immun. 1993 May;61(5):2260–2265. doi: 10.1128/iai.61.5.2260-2265.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Eckmann L., Kagnoff M. F., Fierer J. Epithelial cells secrete the chemokine interleukin-8 in response to bacterial entry. Infect Immun. 1993 Nov;61(11):4569–4574. doi: 10.1128/iai.61.11.4569-4574.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Evans D. G., Evans D. J., Jr, Tjoa W. Hemagglutination of human group A erythrocytes by enterotoxigenic Escherichia coli isolated from adults with diarrhea: correlation with colonization factor. Infect Immun. 1977 Nov;18(2):330–337. doi: 10.1128/iai.18.2.330-337.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gallin J. I., Clark R. A., Kimball H. R. Granulocyte chemotaxis: an improved in vitro assay employing 51 Cr-labeled granulocytes. J Immunol. 1973 Jan;110(1):233–240. [PubMed] [Google Scholar]
  14. Genco R. J., Van Dyke T. E., Levine M. J., Nelson R. D., Wilson M. E. 1985 Kreshover lecture. Molecular factors influencing neutrophil defects in periodontal disease. J Dent Res. 1986 Dec;65(12):1379–1391. doi: 10.1177/00220345860650120201. [DOI] [PubMed] [Google Scholar]
  15. Gothefors L., Ahrén C., Stoll B., Barua D. K., Orskov F., Salek M. A., Svennerholm A. M. Presence of colonization factor antigens on fresh isolates of fecal Escherichia coli: a prospective study. J Infect Dis. 1985 Dec;152(6):1128–1133. doi: 10.1093/infdis/152.6.1128. [DOI] [PubMed] [Google Scholar]
  16. Haffajee A. D., Socransky S. S. Microbial etiological agents of destructive periodontal diseases. Periodontol 2000. 1994 Jun;5:78–111. doi: 10.1111/j.1600-0757.1994.tb00020.x. [DOI] [PubMed] [Google Scholar]
  17. Holt S. C., Ebersole J., Felton J., Brunsvold M., Kornman K. S. Implantation of Bacteroides gingivalis in nonhuman primates initiates progression of periodontitis. Science. 1988 Jan 1;239(4835):55–57. doi: 10.1126/science.3336774. [DOI] [PubMed] [Google Scholar]
  18. Jung H. C., Eckmann L., Yang S. K., Panja A., Fierer J., Morzycka-Wroblewska E., Kagnoff M. F. A distinct array of proinflammatory cytokines is expressed in human colon epithelial cells in response to bacterial invasion. J Clin Invest. 1995 Jan;95(1):55–65. doi: 10.1172/JCI117676. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Luscinskas F. W., Cybulsky M. I., Kiely J. M., Peckins C. S., Davis V. M., Gimbrone M. A., Jr Cytokine-activated human endothelial monolayers support enhanced neutrophil transmigration via a mechanism involving both endothelial-leukocyte adhesion molecule-1 and intercellular adhesion molecule-1. J Immunol. 1991 Mar 1;146(5):1617–1625. [PubMed] [Google Scholar]
  20. Madianos P. N., Papapanou P. N., Nannmark U., Dahlén G., Sandros J. Porphyromonas gingivalis FDC381 multiplies and persists within human oral epithelial cells in vitro. Infect Immun. 1996 Feb;64(2):660–664. doi: 10.1128/iai.64.2.660-664.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Malek R., Fisher J. G., Caleca A., Stinson M., van Oss C. J., Lee J. Y., Cho M. I., Genco R. J., Evans R. T., Dyer D. W. Inactivation of the Porphyromonas gingivalis fimA gene blocks periodontal damage in gnotobiotic rats. J Bacteriol. 1994 Feb;176(4):1052–1059. doi: 10.1128/jb.176.4.1052-1059.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. McCormick B. A., Miller S. I., Carnes D., Madara J. L. Transepithelial signaling to neutrophils by salmonellae: a novel virulence mechanism for gastroenteritis. Infect Immun. 1995 Jun;63(6):2302–2309. doi: 10.1128/iai.63.6.2302-2309.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Meyer D. H., Sreenivasan P. K., Fives-Taylor P. M. Evidence for invasion of a human oral cell line by Actinobacillus actinomycetemcomitans. Infect Immun. 1991 Aug;59(8):2719–2726. doi: 10.1128/iai.59.8.2719-2726.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Miller D. R., Lamster I. B., Chasens A. I. Role of the polymorphonuclear leukocyte in periodontal health and disease. J Clin Periodontol. 1984 Jan;11(1):1–15. doi: 10.1111/j.1600-051x.1984.tb01303.x. [DOI] [PubMed] [Google Scholar]
  25. Miller T. E., Findon G., Cawley S. Cellular basis of host defence in pyelonephritis. III. Deletion of individual components. Br J Exp Pathol. 1987 Jun;68(3):377–388. [PMC free article] [PubMed] [Google Scholar]
  26. Novak M. J., Cohen H. J. Depolarization of polymorphonuclear leukocytes by Porphyromonas (Bacteroides) gingivalis 381 in the absence of respiratory burst activation. Infect Immun. 1991 Sep;59(9):3134–3142. doi: 10.1128/iai.59.9.3134-3142.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Osborn L. Leukocyte adhesion to endothelium in inflammation. Cell. 1990 Jul 13;62(1):3–6. doi: 10.1016/0092-8674(90)90230-c. [DOI] [PubMed] [Google Scholar]
  28. Page R. C., Schroeder H. E. Pathogenesis of inflammatory periodontal disease. A summary of current work. Lab Invest. 1976 Mar;34(3):235–249. [PubMed] [Google Scholar]
  29. Parkos C. A., Colgan S. P., Liang T. W., Nusrat A., Bacarra A. E., Carnes D. K., Madara J. L. CD47 mediates post-adhesive events required for neutrophil migration across polarized intestinal epithelia. J Cell Biol. 1996 Feb;132(3):437–450. doi: 10.1083/jcb.132.3.437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Parkos C. A., Delp C., Arnaout M. A., Madara J. L. Neutrophil migration across a cultured intestinal epithelium. Dependence on a CD11b/CD18-mediated event and enhanced efficiency in physiological direction. J Clin Invest. 1991 Nov;88(5):1605–1612. doi: 10.1172/JCI115473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Rotstein O. D., Nasmith P. E., Grinstein S. The Bacteroides by-product succinic acid inhibits neutrophil respiratory burst by reducing intracellular pH. Infect Immun. 1987 Apr;55(4):864–870. doi: 10.1128/iai.55.4.864-870.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sandros J., Papapanou P. N., Nannmark U., Dahlén G. Porphyromonas gingivalis invades human pocket epithelium in vitro. J Periodontal Res. 1994 Jan;29(1):62–69. doi: 10.1111/j.1600-0765.1994.tb01092.x. [DOI] [PubMed] [Google Scholar]
  33. Sandros J., Papapanou P., Dahlén G. Porphyromonas gingivalis invades oral epithelial cells in vitro. J Periodontal Res. 1993 May;28(3):219–226. doi: 10.1111/j.1600-0765.1993.tb01072.x. [DOI] [PubMed] [Google Scholar]
  34. Savkovic S. D., Koutsouris A., Hecht G. Attachment of a noninvasive enteric pathogen, enteropathogenic Escherichia coli, to cultured human intestinal epithelial monolayers induces transmigration of neutrophils. Infect Immun. 1996 Nov;64(11):4480–4487. doi: 10.1128/iai.64.11.4480-4487.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Springer T. A. Adhesion receptors of the immune system. Nature. 1990 Aug 2;346(6283):425–434. doi: 10.1038/346425a0. [DOI] [PubMed] [Google Scholar]
  36. Sreenivasan P. K., Meyer D. H., Fives-Taylor P. M. Requirements for invasion of epithelial cells by Actinobacillus actinomycetemcomitans. Infect Immun. 1993 Apr;61(4):1239–1245. doi: 10.1128/iai.61.4.1239-1245.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Tai H., Kobayashi T., Hara K. Changes in complement and immunoglobulin G receptor expression on neutrophils associated with Porphyromonas gingivalis-induced inhibition of phagocytosis. Infect Immun. 1993 Aug;61(8):3533–3535. doi: 10.1128/iai.61.8.3533-3535.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Tsujimura S., Otaguro K., Sasaki M., Tanaka R. Chemotactic factors as cause of polyleukocyte urine in urinary tract infection: chemotactic activity of urinary protein fraction. Invest Urol. 1980 Jan;17(4):269–272. [PubMed] [Google Scholar]
  39. Van Dyke T. E., Bartholomew E., Genco R. J., Slots J., Levine M. J. Inhibition of neutrophil chemotaxis by soluble bacterial products. J Periodontol. 1982 Aug;53(8):502–508. doi: 10.1902/jop.1982.53.8.502. [DOI] [PubMed] [Google Scholar]
  40. Van Dyke T. E., Hoop G. A. Neutrophil function and oral disease. Crit Rev Oral Biol Med. 1990;1(2):117–133. doi: 10.1177/10454411900010020201. [DOI] [PubMed] [Google Scholar]
  41. Van Dyke T. E. Neutrophil receptor modulation in the pathogenesis of periodontal diseases. J Dent Res. 1984 Mar;63(3):452–454. doi: 10.1177/00220345840630031701. [DOI] [PubMed] [Google Scholar]
  42. Weiland J. E., Davis W. B., Holter J. F., Mohammed J. R., Dorinsky P. M., Gadek J. E. Lung neutrophils in the adult respiratory distress syndrome. Clinical and pathophysiologic significance. Am Rev Respir Dis. 1986 Feb;133(2):218–225. doi: 10.1164/arrd.1986.133.2.218. [DOI] [PubMed] [Google Scholar]
  43. Yardley J. H., Donowitz M. Colo-rectal biopsy in inflammatory bowel disease. Monogr Pathol. 1977;(18):50–94. [PubMed] [Google Scholar]

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