1887

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Volume 47, Issue 10

Induction of granulomas in interferon-γ gene-disrupted mice by avirulent but not by virulent strains of Free

Abstract

To gain a better understanding of the pathological role of interferon- (IFN-γ) in specific granuloma formation, IFN- gene-deficient mice (BALB/c and C57BL/6) were produced. The IFN- gene in embryonic stem (ES) cells was disrupted by inserting the -galactosidase gene (Z) and the neomycin resistance gene () at the translation initiation site in exon 1 by homologous recombination. Six-week-old IFN--deficient and wild-type mice were inoculated with 10-10 bacilli of various strains of (Kurono, H37Rv, H37Ra and BCG Pasteur) through their tail veins. The mice were examined 7 weeks later for granuloma formation. The avirulent BCG Pasteur and H37Ra strains (10-10 bacilli/ml) induced granulomas in the spleen, liver and lungs of IFN--deficient mice. The granulomas consisted of epithelioid macrophages and Langhans multinucleate giant cells, but lacked caseous necrosis. The virulent Kurono and H37Rv strains induced disseminated abscesses but not granulomas in various organs of IFN--deficient mice and Mac-3-positive macrophages were not detected in the abscess lesions. These results suggest that IFN- may be primarily responsible for macrophage activation and that other factor(s) may be involved in the granuloma formation mechanism.

  • Received:
  • Accepted:
  • Published Online:
© 1998 The Pathological Society of Great Britain and Ireland
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1998-10-01
2024-04-19
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References

  1. Vilcek J., Gray P. W., Rinderknecht E., Sevastopoulos C. G. Interferon γ: a lymphokine for all seasons. Lymphokines 1985; 11:1–32
     [Google Scholar]
  2. Schreiber R. D., Celada A. Molecular characterization of interferon γ as a macrophage activating factor. Lymphokines 1985; 11:87–118
     [Google Scholar]
  3. Mackaness G. B. Cellular resistance to infection. J Exp Med 1962; 116:381–406
     [Google Scholar]
  4. Buchmeier N. A., Schreiber R. D. Requirement of endogenous interferon-γ production for resolution of Listeria monocytogenes infection. Proc Natl Acad Sci USA 1985; 82:7404–7408
     [Google Scholar]
  5. Belosevic M., Davis C. E., Meltzer M. S., Nacy C. A. Regulation of activated macrophage antimicrobial activities. Identification of lymphokines that cooperate with IFN-γ for induction of resistance to infection. J Immunol 1988; 141:890–896
     [Google Scholar]
  6. Murray H. W., Rubin B. Y., Rothermel C. D. Killing of intracellular Leishmania donovani by lymphokine-stimulated human mononuclear phagocytes: evidence that interferon-gamma is the activating lymphokine. J Clin Invest 1983; 72:1506–1510
     [Google Scholar]
  7. Kinderlen A. F., Kaufmann S. H. E., Lohmann-Matthes M.-L. Protection of mice against the intracellular bacterium Listeria monocytogenes by recombinant interferon. Eur J Immunol 1984; 14:964–967
     [Google Scholar]
  8. Barnes P. R., Fong S.-J., Brennan P. J., Twomey P. E., Mazumder A., Modlin R. L. Local production of tumor necrosis factor and IFN-gamma in tuberculous pleuritis. J Immunol 1990; 145:149–154
     [Google Scholar]
  9. Yamamura M., Uyemura K., Deans R. J. Defining protective responses to pathogens: cytokine profiles in leprosy lesions. Science 1991; 254:277–279
     [Google Scholar]
  10. Tagawa Y., Sekikawa K., Iwakura Y. Suppression of concana-valin A-induced hepatitis in IFN-γ −/−, but not in TNF-α −/−, mice: role for IFN-γ in activating apoptosis in hepatocytes. J Immunol 1997; 159:1418–1428
     [Google Scholar]
  11. Taylor A. P., Murray H. W. Intracellular antimicrobial activity in the absence of interferon-γ: effect of interleukin-12 in experimental visceral leishmaniasis in interferon-γ gene-disrupted mice. J Exp Med 1997; 185:1231–1239
     [Google Scholar]
  12. Hsu S. M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 1981; 29:577–580
     [Google Scholar]
  13. Sugawara I., Yamada H., Nakamura H. Preferential expression of the multidrug-resistance-associated protein (MRP) in adenocarcinoma of the lung. Int J Cancer 1995; 64:322–325
     [Google Scholar]
  14. Ralph P., Ho M.-K., Litcofsky P. B., Springer T. A. Expression and induction in vitro of macrophage differentiation antigens on murine cell lines. J Immunol 1983; 130:108–114
     [Google Scholar]
  15. Wilson K. Preparation of genomic DNA from bacteria. In Ausubel F. M., Brent R., Kinston R. E. Current protocols in molecular biology vol 1 New York: Wiley Interscience; 19902.4.1–2.4.2
     [Google Scholar]
  16. Thierry D., Brisson-Noël A., Vincent-Lévy-Frébault V., Nguyen S., Guesdon J.-L., Gicquel B. Characterization of a Mycobacterium tuberculosis insertion sequence, IS 6110, and its application in diagnosis. J Clin Microbiol 1990; 28:2668–2673
     [Google Scholar]
  17. Young D., Lathigra R., Hendrix R., Sweetser D., Young R. A. Stress proteins are immune targets in leprosy and tuberculosis. Proc Natl Acad Sci USA 1988; 85:4267–4270
     [Google Scholar]
  18. Cooper A. M., Dalton D. K., Stewart T. A., Griffin J. P., Russell D. G., Orme I. M. Disseminated tuberculosis in interferon γ gene-disrupted mice. J Exp Med 1993; 178:2243–2247
     [Google Scholar]
  19. Flynn J. L., Chan J., Triebold K. J., Dalton D. K., Stewart T. A., Bloom B. R. An essential role for interleukin γ in the resistance to Mycobacterium tuberculosis infection. J Exp Med 1993; 178:2249–2254
     [Google Scholar]
  20. Murray H., Rubin B. Y., Masur G., Roberts R. B. Impaired production of lymphokines and immune (gamma) interferon in the acquired immunodeficiency syndrome. N Engl J Med 1984; 310:883–889
     [Google Scholar]
  21. Jitsukawa T., Nakajima S., Sugawara I., Mori S., de Ley M. Characterization of murine monoclonal antibodies to human interferon-gamma (IFN-γ) and their application for sandwich enzyme-linked immunosorbent assay (ELISA). Microbiol Immunol 1987; 31:809–820
     [Google Scholar]
  22. Dalton D. K., Pitts-Meek S., Keshav S., Figari I. S., Bradley A., Stewart T. A. Multiple defects of immune cell function in mice with disrupted interferon-y genes. Science 1993; 259:1739–1742
     [Google Scholar]
  23. Kindler V., Sappino A.-P., Grau G. E., Piguet P.-F., Vassali P. The inducing role of tumor necrosis factor in the development of bactericidal granulomas during BCG infection. Cell 1989; 56:731–740
     [Google Scholar]
  24. Amiri P., Locksley R. M., Parslow T. G. Tumor necrosis factor a restores granulomas and induces parasite egg-laying in schistosome-infected SCID mice. Nature 1992; 356:604–607
     [Google Scholar]
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Induction of granulomas in interferon-γ gene-disrupted mice by avirulent but not by virulent strains of Mycobacterium tuberculosis
J. Med. Microbiol. 47, 871 (1998); https://doi.org/10.1099/00222615-47-10-871
/content/journal/jmm/10.1099/00222615-47-10-871
/content/journal/jmm/10.1099/00222615-47-10-871
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