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. 1989 Jan;57(1):225–230. doi: 10.1128/iai.57.1.225-230.1989

Intestinal multiplication of Mycobacterium paratuberculosis in athymic nude gnotobiotic mice.

H L Hamilton 1, D M Follett 1, L M Siegfried 1, C J Czuprynski 1
PMCID: PMC313075  PMID: 2909488

Abstract

In this study gnotobiotic mice were inoculated with a human isolate of Mycobacterium paratuberculosis (strain Linda; ATCC 43015) in an attempt to investigate the pathogenesis of intestinal paratuberculosis. Mycobacterium paratuberculosis-monoassociated nu/+ mice developed a persistent low-level intestinal infection but did not support progressive bacillary multiplication. In contrast, monoassociated nu/nu mice eventually harbored approximately 10(7) M. paratuberculosis per g of intestinal tissue. Acid-fast bacilli and granulomas were observed in the intestinal mucosa and livers of nu/nu but not nu/+ mice. Similar results were obtained after intragastric inoculation of M. paratuberculosis into nu/+ and nu/nu flora-defined mice. These observations suggest that the presence of an intact cellular immune system is important for limiting intestinal multiplication of M. paratuberculosis. The results of this study may be relevant to our understanding of the pathogenesis of Johne's disease in ruminants and of human inflammatory bowel diseases that have a mycobacterial etiology (e.g., some cases of Crohn's disease and Mycobacterium avium-Mycobacterium intracellulare enteritis in patients with acquired immunodeficiency syndrome).

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Selected References

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  1. Bartizal K. F., Salkowski C., Pleasants J. R., Balish E. The effect of microbial flora, diet, and age on the tumoricidal activity of natural killer cells. J Leukoc Biol. 1984 Dec;36(6):739–750. doi: 10.1002/jlb.36.6.739. [DOI] [PubMed] [Google Scholar]
  2. Bendixen P. H., Bloch B., Jorgensen J. B. Lack of intracellular degradation of Mycobacterium paratuberculosis by bovine macrophages infected in vitro and in vivo: light microscopic and electron microscopic observations. Am J Vet Res. 1981 Jan;42(1):109–113. [PubMed] [Google Scholar]
  3. Buergelt C. D., Hall C., McEntee K., Duncan J. R. Pathological evaluation of paratuberculosis in naturally infected cattle. Vet Pathol. 1978 Mar;15(2):196–207. doi: 10.1177/030098587801500206. [DOI] [PubMed] [Google Scholar]
  4. Burnham W. R., Lennard-Jones J. E., Stanford J. L., Bird R. G. Mycobacteria as a possible cause of inflammatory bowel disease. Lancet. 1978 Sep 30;2(8092 Pt 1):693–696. doi: 10.1016/s0140-6736(78)92699-5. [DOI] [PubMed] [Google Scholar]
  5. CHANDLER R. L. Infection of laboratory animals with Mycobacterium johnei. V. Further studies on the comparative susceptibility of C57 black mice. J Comp Pathol. 1962 Apr;72:198–213. doi: 10.1016/s0368-1742(62)80024-1. [DOI] [PubMed] [Google Scholar]
  6. Cave D. R., Mitchell D. N., Brooke B. N. Induction of granulomas in mice by Crohn's disease tissue. Gastroenterology. 1978 Oct;75(4):632–637. [PubMed] [Google Scholar]
  7. Chehl S., Ruby J., Job C. K., Hastings R. C. The growth of Mycobacterium leprae in nude mice. Lepr Rev. 1983 Dec;54(4):283–304. doi: 10.5935/0305-7518.19830035. [DOI] [PubMed] [Google Scholar]
  8. Chiodini R. J., Van Kruiningen H. J., Merkal R. S. Ruminant paratuberculosis (Johne's disease): the current status and future prospects. Cornell Vet. 1984 Jul;74(3):218–262. [PubMed] [Google Scholar]
  9. Chiodini R. J., Van Kruiningen H. J., Merkal R. S., Thayer W. R., Jr, Coutu J. A. Characteristics of an unclassified Mycobacterium species isolated from patients with Crohn's disease. J Clin Microbiol. 1984 Nov;20(5):966–971. doi: 10.1128/jcm.20.5.966-971.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chiodini R. J., Van Kruiningen H. J., Thayer W. R., Coutu J. A. Spheroplastic phase of mycobacteria isolated from patients with Crohn's disease. J Clin Microbiol. 1986 Sep;24(3):357–363. doi: 10.1128/jcm.24.3.357-363.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Chiodini R. J., Van Kruiningen H. J., Thayer W. R., Merkal R. S., Coutu J. A. Possible role of mycobacteria in inflammatory bowel disease. I. An unclassified Mycobacterium species isolated from patients with Crohn's disease. Dig Dis Sci. 1984 Dec;29(12):1073–1079. doi: 10.1007/BF01317078. [DOI] [PubMed] [Google Scholar]
  12. Collins F. M. Mycobacterium avium-complex infections and development of the acquired immunodeficiency syndrome: casual opportunist or causal cofactor? Int J Lepr Other Mycobact Dis. 1986 Sep;54(3):458–474. [PubMed] [Google Scholar]
  13. Czuprynski C. J., Balish E. Pathogenesis of Listeria monocytogenes for gnotobiotic rats. Infect Immun. 1981 Apr;32(1):323–331. doi: 10.1128/iai.32.1.323-331.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Czuprynski C. J., Johnson W. J., Balish E., Wilkins T. Pseudomembranous colitis in Clostridium difficile-monoassociated rats. Infect Immun. 1983 Mar;39(3):1368–1376. doi: 10.1128/iai.39.3.1368-1376.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Damsker B., Bottone E. J. Mycobacterium avium-Mycobacterium intracellulare from the intestinal tracts of patients with the acquired immunodeficiency syndrome: concepts regarding acquisition and pathogenesis. J Infect Dis. 1985 Jan;151(1):179–181. doi: 10.1093/infdis/151.1.179. [DOI] [PubMed] [Google Scholar]
  16. Das K. M., Valenzuela I., Morecki R. Crohn disease lymph node homogenates produce murine lymphoma in athymic mice. Proc Natl Acad Sci U S A. 1980 Jan;77(1):588–592. doi: 10.1073/pnas.77.1.588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Elliott P. R., Lennard-Jones J. E., Burnham W. R., White S., Stanford J. L. Further data on skin testing with mycobacterial antigens in inflammatory bowel disease. Lancet. 1980 Aug 30;2(8192):483–484. doi: 10.1016/s0140-6736(80)91922-4. [DOI] [PubMed] [Google Scholar]
  18. GILMOUR N. J., CAMPBELL J., BROTHERSTON J. G. The pathogenesis of Mycobacterium johnei in orally dosed hamsters. J Comp Pathol. 1963 Apr;73:98–106. doi: 10.1016/s0368-1742(63)80013-2. [DOI] [PubMed] [Google Scholar]
  19. Gitnick G. Is Crohn's disease a mycobacterial disease after all? Dig Dis Sci. 1984 Dec;29(12):1086–1088. doi: 10.1007/BF01317080. [DOI] [PubMed] [Google Scholar]
  20. HIRCH A. Infection of hamsters and rabbits with Mycobacterium johnei. J Comp Pathol. 1956 Jul;66(3):260–269. doi: 10.1016/s0368-1742(56)80027-1. [DOI] [PubMed] [Google Scholar]
  21. Hines S. A., Buergelt C. D., Wilson J. H., Bliss E. L. Disseminated Mycobacterium paratuberculosis infection in a cow. J Am Vet Med Assoc. 1987 Mar 15;190(6):681–683. [PubMed] [Google Scholar]
  22. Kirsner J. B., Shorter R. G. Recent developments in "nonspecific" inflammatory bowel disease (first of two parts). N Engl J Med. 1982 Apr 1;306(13):775–785. doi: 10.1056/NEJM198204013061304. [DOI] [PubMed] [Google Scholar]
  23. Larsen A. B., Miller J. M. Effect of dexamethasone on Mycobacterium paratuberculosis infection in hamsters. Am J Vet Res. 1978 Nov;39(11):1866–1867. [PubMed] [Google Scholar]
  24. Lefford M. J. Mycobacterium lepraemurium infection of nude athymic (nu/nu) mice. Infect Immun. 1985 Jul;49(1):190–196. doi: 10.1128/iai.49.1.190-196.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. McClure H. M., Chiodini R. J., Anderson D. C., Swenson R. B., Thayer W. R., Coutu J. A. Mycobacterium paratuberculosis infection in a colony of stumptail macaques (Macaca arctoides). J Infect Dis. 1987 May;155(5):1011–1019. doi: 10.1093/infdis/155.5.1011. [DOI] [PubMed] [Google Scholar]
  26. McFadden J. J., Butcher P. D., Chiodini R. J., Hermon-Taylor J. Determination of genome size and DNA homology between an unclassified Mycobacterium species isolated from patients with Crohn's disease and other mycobacteria. J Gen Microbiol. 1987 Jan;133(1):211–214. doi: 10.1099/00221287-133-1-211. [DOI] [PubMed] [Google Scholar]
  27. McFadden J. J., Butcher P. D., Chiodini R., Hermon-Taylor J. Crohn's disease-isolated mycobacteria are identical to Mycobacterium paratuberculosis, as determined by DNA probes that distinguish between mycobacterial species. J Clin Microbiol. 1987 May;25(5):796–801. doi: 10.1128/jcm.25.5.796-801.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Patterson D. S., Allen W. M. Chronic mycobacterial enteritis in ruminants as a model of Crohn's disease. Proc R Soc Med. 1972 Nov;65(11):998–1001. doi: 10.1177/003591577206501140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Schneebaum C. W., Novick D. M., Chabon A. B., Strutynsky N., Yancovitz S. R., Freund S. Terminal ileitis associated with Mycobacterium avium-intracellulare infection in a homosexual man with acquired immune deficiency syndrome. Gastroenterology. 1987 May;92(5 Pt 1):1127–1132. doi: 10.1016/s0016-5085(87)91068-7. [DOI] [PubMed] [Google Scholar]
  30. Thayer W. R., Jr, Coutu J. A., Chiodini R. J., Van Kruiningen H. J., Merkal R. S. Possible role of mycobacteria in inflammatory bowel disease. II. Mycobacterial antibodies in Crohn's disease. Dig Dis Sci. 1984 Dec;29(12):1080–1085. doi: 10.1007/BF01317079. [DOI] [PubMed] [Google Scholar]
  31. Van Kruiningen H. J., Chiodini R. J., Thayer W. R., Coutu J. A., Merkal R. S., Runnels P. L. Experimental disease in infant goats induced by a Mycobacterium isolated from a patient with Crohn's disease. A preliminary report. Dig Dis Sci. 1986 Dec;31(12):1351–1360. doi: 10.1007/BF01299814. [DOI] [PubMed] [Google Scholar]
  32. Whorwell P. J. Infectious agents in Crohn's disease-fact or artefact? Scand J Gastroenterol. 1981;16(2):161–166. doi: 10.3109/00365528109181951. [DOI] [PubMed] [Google Scholar]
  33. Yoshimura H. H., Graham D. Y., Estes M. K., Merkal R. S. Investigation of association of mycobacteria with inflammatory bowel disease by nucleic acid hybridization. J Clin Microbiol. 1987 Jan;25(1):45–51. doi: 10.1128/jcm.25.1.45-51.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Young L. S., Inderlied C. B., Berlin O. G., Gottlieb M. S. Mycobacterial infections in AIDS patients, with an emphasis on the Mycobacterium avium complex. Rev Infect Dis. 1986 Nov-Dec;8(6):1024–1033. doi: 10.1093/clinids/8.6.1024. [DOI] [PubMed] [Google Scholar]
  35. Zurbrick B. G., Czuprynski C. J. Ingestion and intracellular growth of Mycobacterium paratuberculosis within bovine blood monocytes and monocyte-derived macrophages. Infect Immun. 1987 Jul;55(7):1588–1593. doi: 10.1128/iai.55.7.1588-1593.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Zurbrick B. G., Follett D. M., Czuprynski C. J. Cytokine regulation of the intracellular growth of Mycobacterium paratuberculosis in bovine monocytes. Infect Immun. 1988 Jul;56(7):1692–1697. doi: 10.1128/iai.56.7.1692-1697.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]

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