Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1997 Sep;65(9):3781–3787. doi: 10.1128/iai.65.9.3781-3787.1997

Increased susceptibility of RAG-2 SCID mice to dissemination of endodontic infections.

R Teles 1, C Y Wang 1, P Stashenko 1
PMCID: PMC175539  PMID: 9284152

Abstract

Specific immunity has been implicated in the pathogenesis of periapical lesions, although the extent to which these mechanisms are actually involved in either protection or destruction of the pulp-periapex complex is yet to be established. To investigate this question we compared periapical-lesion pathogenesis in RAG-2 severe combined immunodeficient (SCID) mice with immunocompetent control mice following surgical pulp exposure. In order to equalize the bacterial challenge, an infection protocol using Prevotella intermedia, Fusobacterium nucleatum, Peptostreptococcus micros, and Streptococcus intermedius was devised. The results demonstrated that after infection, the proportion of the root canal flora represented by the four pathogens was almost identical in both groups (39.9 and 42.2% for RAG-2 and immunocompetent control mice, respectively). The effects of abrogation of T- and B-cell mechanisms on periapical pathogenesis were then assessed. Approximately one-third of the RAG-2 mice developed endodontic abscesses, while no immunocompetent controls had abscesses, results which indicated regional dissemination of the infection. A similar incidence of abscesses was found in two additional experiments. Abscessed RAG-2 teeth had significantly larger periapical lesions than did nonabscessed RAG-2 teeth (P < or = 0.05) and exposed immunocompetent controls (P < or = 0.01), whereas nonabscessed RAG-2 teeth were not significantly different from those of exposed immunocompetent controls in periapical-lesion size. We conclude that B- and T-cell-mediated immunity protects the host from the dissemination of endodontic infections and that RAG-2 mice are more susceptible to infection-induced pulp-periapex destruction.

Full Text

The Full Text of this article is available as a PDF (694.5 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baker P. J., Evans R. T., Roopenian D. C. Oral infection with Porphyromonas gingivalis and induced alveolar bone loss in immunocompetent and severe combined immunodeficient mice. Arch Oral Biol. 1994 Dec;39(12):1035–1040. doi: 10.1016/0003-9969(94)90055-8. [DOI] [PubMed] [Google Scholar]
  2. Barkhordar R. A., Hussain M. Z., Hayashi C. Detection of interleukin-1 beta in human periapical lesions. Oral Surg Oral Med Oral Pathol. 1992 Mar;73(3):334–336. doi: 10.1016/0030-4220(92)90131-9. [DOI] [PubMed] [Google Scholar]
  3. Baumgartner J. C., Falkler W. A., Jr Biosynthesis of IgG in periapical lesion explant cultures. J Endod. 1991 Apr;17(4):143–146. doi: 10.1016/S0099-2399(06)82005-4. [DOI] [PubMed] [Google Scholar]
  4. Baumgartner J. C., Falkler W. A., Jr Reactivity of IgG from explant cultures of periapical lesions with implicated microorganisms. J Endod. 1991 May;17(5):207–212. doi: 10.1016/S0099-2399(06)81922-9. [DOI] [PubMed] [Google Scholar]
  5. Behling U. H., Sallay C., Sanavi F., Pham P. H., Nowotny A. Humoral immunity and reduced periodontal bone loss in Eikenella corrodens-monoassociated rats. Infect Immun. 1981 Sep;33(3):801–805. doi: 10.1128/iai.33.3.801-805.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bergenholtz G., Lekholm U., Liljenberg B., Lindhe J. Morphometric analysis of chronic inflammatory periapical lesions in root-filled teeth. Oral Surg Oral Med Oral Pathol. 1983 Mar;55(3):295–301. doi: 10.1016/0030-4220(83)90331-6. [DOI] [PubMed] [Google Scholar]
  7. Burckhardt J. J., Gaegauf-Zollinger R., Schmid R., Guggenheim B. Alveolar bone loss in rats after immunization with Actinomyces viscosus. Infect Immun. 1981 Mar;31(3):971–977. doi: 10.1128/iai.31.3.971-977.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Crawford J. M., Taubman M. A., Smith D. J. The effects of local immunization with periodontopathic microorganisms on periodontal bone loss in gnotobiotic rats. J Periodontal Res. 1978 Sep;13(5):445–459. doi: 10.1111/j.1600-0765.1978.tb00198.x. [DOI] [PubMed] [Google Scholar]
  9. Dahlén G., Fabricius L., Heyden G., Holm S. E., Möller A. J. Apical periodontitis induced by selected bacterial strains in root canals of immunized and nonimmunized monkeys. Scand J Dent Res. 1982 Jun;90(3):207–216. doi: 10.1111/j.1600-0722.1982.tb00729.x. [DOI] [PubMed] [Google Scholar]
  10. Ebersole J. L., Brunsvold M., Steffensen B., Wood R., Holt S. C. Effects of immunization with Porphyromonas gingivalis and Prevotella intermedia on progression of ligature-induced periodontitis in the nonhuman primate Macaca fascicularis. Infect Immun. 1991 Oct;59(10):3351–3359. doi: 10.1128/iai.59.10.3351-3359.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Evans R. T., Klausen B., Genco R. J. Immunization with fimbrial protein and peptide protects against Porphyromonas gingivalis-induced periodontal tissue destruction. Adv Exp Med Biol. 1992;327:255–262. doi: 10.1007/978-1-4615-3410-5_27. [DOI] [PubMed] [Google Scholar]
  12. Gunaratnam M., Smith G. L., Socransky S. S., Smith C. M., Haffajee A. D. Enumeration of subgingival species on primary isolation plates using colony lifts. Oral Microbiol Immunol. 1992 Feb;7(1):14–18. doi: 10.1111/j.1399-302x.1992.tb00013.x. [DOI] [PubMed] [Google Scholar]
  13. Holt S. C., Brunsvold M., Jones A., Wood R., Ebersole J. L. Cell envelope and cell wall immunization of Macaca fascicularis: effect on the progression of ligature-induced periodontitis. Oral Microbiol Immunol. 1995 Dec;10(6):321–333. doi: 10.1111/j.1399-302x.1995.tb00162.x. [DOI] [PubMed] [Google Scholar]
  14. Kettering J. D., Torabinejad M. Concentrations of immune complexes, IgG, IgM, IgE, and C3 in patients with acute apical abscesses. J Endod. 1984 Sep;10(9):417–421. doi: 10.1016/S0099-2399(84)80262-9. [DOI] [PubMed] [Google Scholar]
  15. Kettering J. D., Torabinejad M., Jones S. L. Specificity of antibodies present in human periapical lesions. J Endod. 1991 May;17(5):213–216. doi: 10.1016/S0099-2399(06)81923-0. [DOI] [PubMed] [Google Scholar]
  16. Klausen B., Evans R. T., Ramamurthy N. S., Golub L. M., Sfintescu C., Lee J. Y., Bedi G., Zambon J. J., Genco R. J. Periodontal bone level and gingival proteinase activity in gnotobiotic rats immunized with Bacteroides gingivalis. Oral Microbiol Immunol. 1991 Aug;6(4):193–201. doi: 10.1111/j.1399-302x.1991.tb00477.x. [DOI] [PubMed] [Google Scholar]
  17. Kontiainen S., Ranta H., Lautenschlager I. Cells infiltrating human periapical inflammatory lesions. J Oral Pathol. 1986 Nov;15(10):544–546. doi: 10.1111/j.1600-0714.1986.tb00574.x. [DOI] [PubMed] [Google Scholar]
  18. Kopp W., Schwarting R. Differentiation of T lymphocyte subpopulations, macrophages, and HLA-DR-restricted cells of apical granulation tissue. J Endod. 1989 Feb;15(2):72–75. doi: 10.1016/S0099-2399(89)80111-6. [DOI] [PubMed] [Google Scholar]
  19. Lewis M. A., MacFarlane T. W., McGowan D. A. Quantitative bacteriology of acute dento-alveolar abscesses. J Med Microbiol. 1986 Mar;21(2):101–104. doi: 10.1099/00222615-21-2-101. [DOI] [PubMed] [Google Scholar]
  20. Lim G. C., Torabinejad M., Kettering J., Linkhardt T. A., Finkelman R. D. Interleukin 1-beta in symptomatic and asymptomatic human periradicular lesions. J Endod. 1994 May;20(5):225–227. doi: 10.1016/S0099-2399(06)80282-7. [DOI] [PubMed] [Google Scholar]
  21. Matsuo T., Ebisu S., Nakanishi T., Yonemura K., Harada Y., Okada H. Interleukin-1 alpha and interleukin-1 beta periapical exudates of infected root canals: correlations with the clinical findings of the involved teeth. J Endod. 1994 Sep;20(9):432–435. doi: 10.1016/s0099-2399(06)80032-4. [DOI] [PubMed] [Google Scholar]
  22. Matsuo T., Nakanishi T., Ebisu S. Immunoglobulins in periapical exudates of infected root canals: correlations with the clinical findings of the involved teeth. Endod Dent Traumatol. 1995 Apr;11(2):95–99. doi: 10.1111/j.1600-9657.1995.tb00466.x. [DOI] [PubMed] [Google Scholar]
  23. Nilsen R., Johannessen A. C., Skaug N., Matre R. In situ characterization of mononuclear cells in human dental periapical inflammatory lesions using monoclonal antibodies. Oral Surg Oral Med Oral Pathol. 1984 Aug;58(2):160–165. doi: 10.1016/0030-4220(84)90131-2. [DOI] [PubMed] [Google Scholar]
  24. Persson G. R., Engel D., Whitney C., Darveau R., Weinberg A., Brunsvold M., Page R. C. Immunization against Porphyromonas gingivalis inhibits progression of experimental periodontitis in nonhuman primates. Infect Immun. 1994 Mar;62(3):1026–1031. doi: 10.1128/iai.62.3.1026-1031.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Sallay K., Sanavi F., Ring I., Pham P., Behling U. H., Nowotny A. Alveolar bone destruction in the immunosuppressed rat. J Periodontal Res. 1982 May;17(3):263–274. doi: 10.1111/j.1600-0765.1982.tb01153.x. [DOI] [PubMed] [Google Scholar]
  27. Samejima Y., Ebisu S., Okada H. Effect of infection with Eikenella corrodens on the progression of ligature-induced periodontitis in rats. J Periodontal Res. 1990 Sep;25(5):308–315. doi: 10.1111/j.1600-0765.1990.tb00920.x. [DOI] [PubMed] [Google Scholar]
  28. Shinkai Y., Rathbun G., Lam K. P., Oltz E. M., Stewart V., Mendelsohn M., Charron J., Datta M., Young F., Stall A. M. RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement. Cell. 1992 Mar 6;68(5):855–867. doi: 10.1016/0092-8674(92)90029-c. [DOI] [PubMed] [Google Scholar]
  29. Stern M. H., Dreizen S., Mackler B. F., Levy B. M. [Antibody-producing cells in human periapical granulomas and cysts]. J Endod. 1981 Oct;7(10):447–452. doi: 10.1016/S0099-2399(81)80304-4. [DOI] [PubMed] [Google Scholar]
  30. Stern M. H., Dreizen S., Mackler B. F., Selbst A. G., Levy B. M. Quantitative analysis of cellular composition of human periapical granuloma. J Endod. 1981 Mar;7(3):117–122. doi: 10.1016/S0099-2399(81)80125-2. [DOI] [PubMed] [Google Scholar]
  31. Tani-Ishii N., Wang C. Y., Stashenko P. Immunolocalization of bone-resorptive cytokines in rat pulp and periapical lesions following surgical pulp exposure. Oral Microbiol Immunol. 1995 Aug;10(4):213–219. doi: 10.1111/j.1399-302x.1995.tb00145.x. [DOI] [PubMed] [Google Scholar]
  32. Tani N., Kuchiba K., Osada T., Watanabe Y., Umemoto T. Effect of T-cell deficiency on the formation of periapical lesions in mice: histological comparison between periapical lesion formation in BALB/c and BALB/c nu/nu mice. J Endod. 1995 Apr;21(4):195–199. doi: 10.1016/s0099-2399(06)80565-0. [DOI] [PubMed] [Google Scholar]
  33. Taubman M. A., Yoshie H., Wetherell J. R., Jr, Ebersole J. L., Smith D. J. Immune response and periodontal bone loss in germfree rats immunized and infected with Actinobacillus actinomycetemcomitans. J Periodontal Res. 1983 Jul;18(4):393–401. doi: 10.1111/j.1600-0765.1983.tb00375.x. [DOI] [PubMed] [Google Scholar]
  34. Torabinejad M., Eby W. C., Naidorf I. J. Inflammatory and immunological aspects of the pathogenesis of human periapical lesions. J Endod. 1985 Nov;11(11):479–488. doi: 10.1016/S0099-2399(85)80221-1. [DOI] [PubMed] [Google Scholar]
  35. Torabinejade M., Kettering J. D. Detection of immune complexes in human dental periapical lesions by anticomplement immunofluorescence technique. Oral Surg Oral Med Oral Pathol. 1979 Sep;48(3):256–261. doi: 10.1016/0030-4220(79)90014-8. [DOI] [PubMed] [Google Scholar]
  36. Torres J. O., Torabinejad M., Matiz R. A., Mantilla E. G. Presence of secretory IgA in human periapical lesions. J Endod. 1994 Feb;20(2):87–89. doi: 10.1016/S0099-2399(06)81188-X. [DOI] [PubMed] [Google Scholar]
  37. Wallstrom J. B., Torabinejad M., Kettering J., McMillan P. Role of T cells in the pathogenesis of periapical lesions. A preliminary report. Oral Surg Oral Med Oral Pathol. 1993 Aug;76(2):213–218. doi: 10.1016/0030-4220(93)90207-k. [DOI] [PubMed] [Google Scholar]
  38. Wang C. Y., Stashenko P. Characterization of bone-resorbing activity in human periapical lesions. J Endod. 1993 Mar;19(3):107–111. doi: 10.1016/S0099-2399(06)80503-0. [DOI] [PubMed] [Google Scholar]
  39. Yamasaki M., Kumazawa M., Kohsaka T., Nakamura H. Effect of methotrexate-induced neutropenia on rat periapical lesion. Oral Surg Oral Med Oral Pathol. 1994 Jun;77(6):655–661. doi: 10.1016/0030-4220(94)90330-1. [DOI] [PubMed] [Google Scholar]
  40. Yanagisawa S. Pathologic study of periapical lesions 1. Periapical granulomas: clinical, histopathologic and immunohistopathologic studies. J Oral Pathol. 1980 Sep;9(5):288–300. doi: 10.1111/j.1600-0714.1980.tb00386.x. [DOI] [PubMed] [Google Scholar]
  41. Yoshinari N., Kameyama Y., Aoyama Y., Nishiyama H., Noguchi T. Effect of long-term methotrexate-induced neutropenia on experimental periodontal lesion in rats. J Periodontal Res. 1994 Nov;29(6):393–400. doi: 10.1111/j.1600-0765.1994.tb01240.x. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES