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. 1995 Jun;63(6):2243–2247. doi: 10.1128/iai.63.6.2243-2247.1995

Growth of Mycobacterium tuberculosis in BCG-resistant and -susceptible mice: establishment of latency and reactivation.

D H Brown 1, B A Miles 1, B S Zwilling 1
PMCID: PMC173292  PMID: 7768604

Abstract

Growth of mycobacterial species is controlled by a gene, Bcg (candidate Nramp). Bcg acts at the macrophage level and is thought to control some aspect of macrophage priming for activation. Infection of Mycobacterium bovis BCG-susceptible (Bcgs) mice with several different mycobacterial species results in the growth of the microorganisms, while the growth of the same organisms is controlled in BCG-resistant (Bcgr) mice. The capacity of Bcg to control the growth of M. tuberculosis has not been extensively explored. The purpose of this investigation, therefore, was to compare the growth of M. tuberculosis in Bcgr and Bcgs mice. We found that the growth of tubercule bacilli was different in the lungs and spleens of Bcgr and Bcgs mice when they were inoculated with fewer then 10(3) CFU of the mycobacterium. The differences in growth were more easily distinguished in the lungs then in the spleens. The growth of the microorganisms in both strains of mice peaked between 35 and 43 days, and a latent infection was established by 65 days after infection. Activation of the hypothalamic-pituitary-adrenal axis resulted in reactivation of the growth of M. tuberculosis in both Bcgr and Bcgs mice. Greater numbers of tubercule bacilli were isolated from lungs than from spleens following reactivation. The utility of this mouse model in the study of the establishment of latency and reactivation of M. tuberculosis is discussed.

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Selected References

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  1. Barton C. H., White J. K., Roach T. I., Blackwell J. M. NH2-terminal sequence of macrophage-expressed natural resistance-associated macrophage protein (Nramp) encodes a proline/serine-rich putative Src homology 3-binding domain. J Exp Med. 1994 May 1;179(5):1683–1687. doi: 10.1084/jem.179.5.1683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Blackwell J. M., Roach T. I., Kiderlen A., Kaye P. M. Role of Lsh in regulating macrophage priming/activation. Res Immunol. 1989 Oct;140(8):798–805. doi: 10.1016/0923-2494(89)90036-9. [DOI] [PubMed] [Google Scholar]
  3. Brown D. H., Sheridan J., Pearl D., Zwilling B. S. Regulation of mycobacterial growth by the hypothalamus-pituitary-adrenal axis: differential responses of Mycobacterium bovis BCG-resistant and -susceptible mice. Infect Immun. 1993 Nov;61(11):4793–4800. doi: 10.1128/iai.61.11.4793-4800.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brown D. H., Zwilling B. S. Activation of the hypothalamic-pituitary-adrenal axis differentially affects the anti-mycobacterial activity of macrophages from BCG-resistant and susceptible mice. J Neuroimmunol. 1994 Sep;53(2):181–187. doi: 10.1016/0165-5728(94)90028-0. [DOI] [PubMed] [Google Scholar]
  5. Cellier M., Govoni G., Vidal S., Kwan T., Groulx N., Liu J., Sanchez F., Skamene E., Schurr E., Gros P. Human natural resistance-associated macrophage protein: cDNA cloning, chromosomal mapping, genomic organization, and tissue-specific expression. J Exp Med. 1994 Nov 1;180(5):1741–1752. doi: 10.1084/jem.180.5.1741. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cox J. H., Knight B. C., Ivanyi J. Mechanisms of recrudescence of Mycobacterium bovis BCG infection in mice. Infect Immun. 1989 Jun;57(6):1719–1724. doi: 10.1128/iai.57.6.1719-1724.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Crocker P. R., Davies E. V., Blackwell J. M. Variable expression of the murine natural resistance gene Lsh in different macrophage populations infected in vitro with Leishmania donovani. Parasite Immunol. 1987 Nov;9(6):705–719. doi: 10.1111/j.1365-3024.1987.tb00540.x. [DOI] [PubMed] [Google Scholar]
  8. Daynes R. A., Meikle A. W., Araneo B. A. Locally active steroid hormones may facilitate compartmentalization of immunity by regulating the types of lymphokines produced by helper T cells. Res Immunol. 1991 Jan;142(1):40–45. doi: 10.1016/0923-2494(91)90010-g. [DOI] [PubMed] [Google Scholar]
  9. Denis M., Forget A., Pelletier M., Gervais F., Skamene E. Killing of Mycobacterium smegmatis by macrophages from genetically susceptible and resistant mice. J Leukoc Biol. 1990 Jan;47(1):25–30. doi: 10.1002/jlb.47.1.25. [DOI] [PubMed] [Google Scholar]
  10. Goto Y., Buschman E., Skamene E. Regulation of host resistance to Mycobacterium intracellulare in vivo and in vitro by the Bcg gene. Immunogenetics. 1989;30(3):218–221. doi: 10.1007/BF02421210. [DOI] [PubMed] [Google Scholar]
  11. Griffin J. P., Orme I. M. Evolution of CD4 T-cell subsets following infection of naive and memory immune mice with Mycobacterium tuberculosis. Infect Immun. 1994 May;62(5):1683–1690. doi: 10.1128/iai.62.5.1683-1690.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gros P., Skamene E., Forget A. Cellular mechanisms of genetically controlled host resistance to Mycobacterium bovis (BCG). J Immunol. 1983 Oct;131(4):1966–1972. [PubMed] [Google Scholar]
  13. Gros P., Skamene E., Forget A. Genetic control of natural resistance to Mycobacterium bovis (BCG) in mice. J Immunol. 1981 Dec;127(6):2417–2421. [PubMed] [Google Scholar]
  14. Kramnik I., Radzioch D., Skamene E. T-helper 1-like subset selection in Mycobacterium bovis bacillus Calmette-Guérin-infected resistant and susceptible mice. Immunology. 1994 Apr;81(4):618–625. [PMC free article] [PubMed] [Google Scholar]
  15. Musa S. A., Kim Y., Hashim R., Wang G. Z., Dimmer C., Smith D. W. Response of inbred mice to aerosol challenge with Mycobacterium tuberculosis. Infect Immun. 1987 Aug;55(8):1862–1866. doi: 10.1128/iai.55.8.1862-1866.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Orme I. M. Characteristics and specificity of acquired immunologic memory to Mycobacterium tuberculosis infection. J Immunol. 1988 May 15;140(10):3589–3593. [PubMed] [Google Scholar]
  17. Orme I. M., Collins F. M. Demonstration of acquired resistance in Bcgr inbred mouse strains infected with a low dose of BCG montreal. Clin Exp Immunol. 1984 Apr;56(1):81–88. [PMC free article] [PubMed] [Google Scholar]
  18. Orme I. M., Stokes R. W., Collins F. M. Genetic control of natural resistance to nontuberculous mycobacterial infections in mice. Infect Immun. 1986 Oct;54(1):56–62. doi: 10.1128/iai.54.1.56-62.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Orme I. M. The kinetics of emergence and loss of mediator T lymphocytes acquired in response to infection with Mycobacterium tuberculosis. J Immunol. 1987 Jan 1;138(1):293–298. [PubMed] [Google Scholar]
  20. Potter M., O'Brien A. D., Skamene E., Gros P., Forget A., Kongshavn P. A., Wax J. S. A BALB/c congenic strain of mice that carries a genetic locus (Ityr) controlling resistance to intracellular parasites. Infect Immun. 1983 Jun;40(3):1234–1235. doi: 10.1128/iai.40.3.1234-1235.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Skamene E., Gros P., Forget A., Kongshavn P. A., St Charles C., Taylor B. A. Genetic regulation of resistance to intracellular pathogens. Nature. 1982 Jun 10;297(5866):506–509. doi: 10.1038/297506a0. [DOI] [PubMed] [Google Scholar]
  22. Stokes R. W., Collins F. M. Growth of Mycobacterium avium in activated macrophages harvested from inbred mice with differing innate susceptibilities to mycobacterial infection. Infect Immun. 1988 Sep;56(9):2250–2254. doi: 10.1128/iai.56.9.2250-2254.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Stokes R. W., Orme I. M., Collins F. M. Role of mononuclear phagocytes in expression of resistance and susceptibility to Mycobacterium avium infections in mice. Infect Immun. 1986 Dec;54(3):811–819. doi: 10.1128/iai.54.3.811-819.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Taylor B. A., O'Brien A. D. Position on mouse chromosome 1 of a gene that controls resistance to Salmonella typhimurium. Infect Immun. 1982 Jun;36(3):1257–1260. doi: 10.1128/iai.36.3.1257-1260.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Vidal S. M., Malo D., Vogan K., Skamene E., Gros P. Natural resistance to infection with intracellular parasites: isolation of a candidate for Bcg. Cell. 1993 May 7;73(3):469–485. doi: 10.1016/0092-8674(93)90135-d. [DOI] [PubMed] [Google Scholar]
  26. Zwilling B. S., Hilburger M. E. Macrophage resistance genes: Bcg/Ity/Lsh. Immunol Ser. 1994;60:233–245. [PubMed] [Google Scholar]

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