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. 1988 Jan;56(1):122–127. doi: 10.1128/iai.56.1.122-127.1988

Immunosuppressive properties of Actinobacillus actinomycetemcomitans leukotoxin.

G Rabie 1, E T Lally 1, B J Shenker 1
PMCID: PMC259245  PMID: 3335399

Abstract

Actinobacillus actinomycetemcomitans produces a leukotoxin that kills human polymorphonuclear cells (PMNs) and monocytes but not lymphocytes. In this study, we examined A. actinomycetemcomitans leukotoxin for its ability to alter human peripheral blood lymphocyte (HPBL) responsiveness. After a 90-min exposure to the leukotoxin, all monocytes were killed and HPBL responsiveness to mitogens and antigens was significantly inhibited. The ability of the leukotoxin to inhibit HPBL responses was not surprising, since monocytes and macrophages are required for many lymphocyte functions. However, we were unable to totally restore HPBL responsiveness when adherent autologous monocytes were added back to cultures of leukotoxin-treated lymphocytes. These studies demonstrate that A. actinomycetemcomitans leukotoxin may also exert nonlethal effects directly on lymphocytes. Furthermore, impaired lymphocyte function did not appear to be the result of indirect effects of products released by dying monocytes. Although it is not clear how A. actinomycetemcomitans acts to cause disease, several investigators have proposed that impaired host defenses may play a pivotal role. Several studies have demonstrated defects in PMN, monocyte, and lymphocyte function in patients with periodontal disease. These findings, along with the data presented in this paper, support the hypothesis that patients who harbor A. actinomycetemcomitans could suffer from local or systemic immune suppression. The effects of this suppression may be to enhance the pathogenicity of A. actinomycetemcomitans itself or that of some other opportunistic organism.

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Selected References

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  1. Baehni P. C., Tsai C. C., McArthur W. P., Hammond B. F., Shenker B. J., Taichman N. S. Leukotoxic activity in different strains of the bacterium Actinobacillus actinomycetemcomitans isolated from juvenile periodontitis in man. Arch Oral Biol. 1981;26(8):671–676. doi: 10.1016/0003-9969(81)90164-3. [DOI] [PubMed] [Google Scholar]
  2. Baehni P., Tsai C. C., McArthur W. P., Hammond B. F., Taichman N. S. Interaction of inflammatory cells and oral microorganisms. VIII. Detection of leukotoxic activity of a plaque-derived gram-negative microorganism. Infect Immun. 1979 Apr;24(1):233–243. doi: 10.1128/iai.24.1.233-243.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barefoot D. H., Silverman M. S. Alveolar bone loss in thymectomized golden hamsters. J Periodontol. 1977 Nov;48(11):699–704. doi: 10.1902/jop.1977.48.11.699. [DOI] [PubMed] [Google Scholar]
  4. Block P. J., Yoran C., Fox A. C., Kaltman A. J. Actinobacillus actinomycetemcomitans endocarditis: report of a case and review of the literature. Am J Med Sci. 1973 Nov;266(5):387–392. doi: 10.1097/00000441-197311000-00006. [DOI] [PubMed] [Google Scholar]
  5. Bolton R. W., Dyer J. K. Suppression of murine lymphocyte mitogen responses by exopolysaccharide from Capnocytophaga ochracea. Infect Immun. 1983 Jan;39(1):476–479. doi: 10.1128/iai.39.1.476-479.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Budtz-Jörgensen E., Kelstrup J., Funder-Nielsen T. D., Knudsen A. M. Leukocyte migration inhibition by bacterial antigens in patients with periodontal disease. J Periodontal Res. 1977 Jan;12(1):21–29. doi: 10.1111/j.1600-0765.1977.tb00105.x. [DOI] [PubMed] [Google Scholar]
  7. DiRienzo J. M., Tsai C. C., Shenker B. J., Taichman N. S., Lally E. T. Monoclonal antibodies to leukotoxin of Actinobacillus actinomycetemcomitans. Infect Immun. 1985 Jan;47(1):31–36. doi: 10.1128/iai.47.1.31-36.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Garner J. G. Isolation of Actinobacillus actinomycetemcomitans and Haemophilus aphrophilus at Auckland Hospital. N Z Med J. 1979 May 23;89(636):384–386. [PubMed] [Google Scholar]
  9. Gaumer H. R., Schwab J. H. Differential susceptibility of mouse lymphocytes to an immunosuppressant from group A streptococci. Cell Immunol. 1972 Aug;4(4):394–406. doi: 10.1016/0008-8749(72)90041-x. [DOI] [PubMed] [Google Scholar]
  10. Kamen P. R. Inhibition of keratinocyte proliferation by extracts of Actinobacillus actinomycetemcomitans. Infect Immun. 1983 Dec;42(3):1191–1194. doi: 10.1128/iai.42.3.1191-1194.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kiley P., Holt S. C. Characterization of the lipopolysaccharide from Actinobacillus actinomycetemcomitans Y4 and N27. Infect Immun. 1980 Dec;30(3):862–873. doi: 10.1128/iai.30.3.862-873.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lane H. C., Volkman D. J., Whalen G., Fauci A. S. In vitro antigen-induced, antigen-specific antibody production in man. Specific and polyclonal components, kinetics, and cellular requirements. J Exp Med. 1981 Oct 1;154(4):1043–1057. doi: 10.1084/jem.154.4.1043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lehner T., Wilton J. M., Ivanyi L., Manson J. D. Immunological aspects of juvenile periodontitis (periodontosis). J Periodontal Res. 1974;9(5):261–272. doi: 10.1111/j.1600-0765.1974.tb00681.x. [DOI] [PubMed] [Google Scholar]
  14. McArthur W. P., Tsai C. C., Baehni P. C., Genco R. J., Taichman N. S. Leukotoxic effects of Actinobacillus actinomycetemcomitans. Modulation by serum components. J Periodontal Res. 1981 Mar;16(2):159–170. doi: 10.1111/j.1600-0765.1981.tb00962.x. [DOI] [PubMed] [Google Scholar]
  15. Metzger Z., Hoffeld J. T., Oppenheim J. J. Regulation by PGE2 of the production of oxygen intermediates by LPS-activated macrophages. J Immunol. 1981 Sep;127(3):1109–1113. [PubMed] [Google Scholar]
  16. Nossal G. J. Current concepts: immunology. The basic components of the immune system. N Engl J Med. 1987 May 21;316(21):1320–1325. doi: 10.1056/NEJM198705213162107. [DOI] [PubMed] [Google Scholar]
  17. Page M. I., King E. O. Infection due to Actinobacillus actinomycetemcomitans and Haemophilus aphrophilus. N Engl J Med. 1966 Jul 28;275(4):181–188. doi: 10.1056/NEJM196607282750403. [DOI] [PubMed] [Google Scholar]
  18. Rylander H., Lindhe J., Ahlstedt S. Experimental gingivitis in immunized dogs. J Periodontal Res. 1976 Nov;11(6):339–348. doi: 10.1111/j.1600-0765.1976.tb00088.x. [DOI] [PubMed] [Google Scholar]
  19. Sallay K., Listgarten M., Sanavi F., Ring I., Nowotny A. Bacterial invasion of oral tissues of immunosuppressed rats. Infect Immun. 1984 Mar;43(3):1091–1093. doi: 10.1128/iai.43.3.1091-1093.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Schwab J. H. Suppression of the immune response by microorganisms. Bacteriol Rev. 1975 Jun;39(2):121–143. doi: 10.1128/br.39.2.121-143.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Seymour G. J., Cole K. L., Powell R. N. Analysis of lymphocyte populations extracted from chronically inflamed human periodontal tissues. II. Blastogenic response. J Periodontal Res. 1985 Nov;20(6):571–579. doi: 10.1111/j.1600-0765.1985.tb00841.x. [DOI] [PubMed] [Google Scholar]
  22. Shenker B. J., Berthold P., Dougherty P., Porter K. K. Immunosuppressive effects of Centipeda periodontii: selective cytotoxicity for lymphocytes and monocytes. Infect Immun. 1987 Oct;55(10):2332–2340. doi: 10.1128/iai.55.10.2332-2340.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Shenker B. J., DiRienzo J. M. Suppression of human peripheral blood lymphocytes by Fusobacterium nucleatum. J Immunol. 1984 May;132(5):2357–2362. [PubMed] [Google Scholar]
  24. Shenker B. J., Kushner M. E., Tsai C. C. Inhibition of fibroblast proliferation by Actinobacillus actinomycetemcomitans. Infect Immun. 1982 Dec;38(3):986–992. doi: 10.1128/iai.38.3.986-992.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Shenker B. J., Listgarten M. A., Taichman N. S. Suppression of human lymphocyte responses by oral spirochetes: a monocyte-dependent phenomenon. J Immunol. 1984 Apr;132(4):2039–2045. [PubMed] [Google Scholar]
  26. Shenker B. J., McArthur W. P., Tsai C. C. Immune suppression induced by Actinobacillus actinomycetemcomitans. I. Effects on human peripheral blood lymphocyte responses to mitogens and antigens. J Immunol. 1982 Jan;128(1):148–154. [PubMed] [Google Scholar]
  27. Shenker B. J., Tsai C. C., Taichman N. S. Suppression of lymphocyte responses by Actinobacillus actinomycetemcomitans. J Periodontal Res. 1982 Sep;17(5):462–465. doi: 10.1111/j.1600-0765.1982.tb02027.x. [DOI] [PubMed] [Google Scholar]
  28. Shenker B. J., Willoughby W. F., Hollingdale M. R., Mann T. N. In vivo responses to inhaled proteins. III. Inhibition of experimental immune complex pneumonitis after suppression of peripheral blood lymphocytes. J Immunol. 1980 Apr;124(4):1763–1772. [PubMed] [Google Scholar]
  29. Stashenko P., Resmini L. M., Haffajee A. D., Socransky S. S. T cell responses of periodontal disease patients and healthy subjects to oral microorganisms. J Periodontal Res. 1983 Nov;18(6):587–600. doi: 10.1111/j.1600-0765.1983.tb00396.x. [DOI] [PubMed] [Google Scholar]
  30. Taichman N. S., Dean R. T., Sanderson C. J. Biochemical and morphological characterization of the killing of human monocytes by a leukotoxin derived from Actinobacillus actinomycetemcomitans. Infect Immun. 1980 Apr;28(1):258–268. doi: 10.1128/iai.28.1.258-268.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Taichman N. S., Klass J. E., Shenker B. J., Macarak E. J., Boehringer H., Tsai C. C. Suspected periodontopathic organisms alter in vitro proliferation of endothelial cells. J Periodontal Res. 1984 Nov;19(6):583–586. doi: 10.1111/j.1600-0765.1984.tb01319.x. [DOI] [PubMed] [Google Scholar]
  32. Tew J. G., Marshall D. R., Moore W. E., Best A. M., Palcanis K. G., Ranney R. R. Serum antibody reactive with predominant organisms in the subgingival flora of young adults with generalized severe periodontitis. Infect Immun. 1985 May;48(2):303–311. doi: 10.1128/iai.48.2.303-311.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Tew J. G., Smibert R. M., Scott E. A., Burmeister J. A., Ranney R. R. Serum antibodies in young adult humans reactive with periodontitis associated treponemes. J Periodontal Res. 1985 Nov;20(6):580–590. doi: 10.1111/j.1600-0765.1985.tb00842.x. [DOI] [PubMed] [Google Scholar]
  34. Thiele D. L., Kurosaka M., Lipsky P. E. Phenotype of the accessory cell necessary for mitogen-stimulated T and B cell responses in human peripheral blood: delineation by its sensitivity to the lysosomotropic agent, L-leucine methyl ester. J Immunol. 1983 Nov;131(5):2282–2290. [PubMed] [Google Scholar]
  35. Tsai C. C., Shenker B. J., DiRienzo J. M., Malamud D., Taichman N. S. Extraction and isolation of a leukotoxin from Actinobacillus actinomycetemcomitans with polymyxin B. Infect Immun. 1984 Feb;43(2):700–705. doi: 10.1128/iai.43.2.700-705.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Unanue E. R., Allen P. M. The basis for the immunoregulatory role of macrophages and other accessory cells. Science. 1987 May 1;236(4801):551–557. doi: 10.1126/science.2437650. [DOI] [PubMed] [Google Scholar]
  37. Vandepitte J., De Geest H., Jousten P. Subacute bacterial endocarditis due to Actinobacillus actinomycetemcomitans. Report of a case with a review of the literature. J Clin Pathol. 1977 Sep;30(9):842–846. doi: 10.1136/jcp.30.9.842. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Vischer T. L., LoSpalluto J. J. The differential effect of cholera toxin on the lymphocyte stimulation induced by various mitogens. Immunology. 1975 Aug;29(2):275–282. [PMC free article] [PubMed] [Google Scholar]
  39. Weir D. M., Blackwell C. C. Interaction of bacteria with the immune system. J Clin Lab Immunol. 1983 Jan;10(1):1–12. [PubMed] [Google Scholar]
  40. Yoshie H., Taubman M. A., Ebersole J. L., Olson C. L., Smith D. J., Pappo J. Activation of rat B lymphocytes by Actinobacillus actinomycetemcomitans. Infect Immun. 1985 Jan;47(1):264–270. doi: 10.1128/iai.47.1.264-270.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Zagury D., Bernard J., Leonard R., Cheynier R., Feldman M., Sarin P. S., Gallo R. C. Long-term cultures of HTLV-III--infected T cells: a model of cytopathology of T-cell depletion in AIDS. Science. 1986 Feb 21;231(4740):850–853. doi: 10.1126/science.2418502. [DOI] [PubMed] [Google Scholar]
  42. Zambon J. J. Actinobacillus actinomycetemcomitans in human periodontal disease. J Clin Periodontol. 1985 Jan;12(1):1–20. doi: 10.1111/j.1600-051x.1985.tb01348.x. [DOI] [PubMed] [Google Scholar]

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