Influence of trehalose 6,6′-dimycolate (TDM) during mycobacterial infection of bone marrow macrophages Free

Abstract

The relative role of surface lipids in the innate macrophage response to infection with mycobacteria remains unknown. Trehalose 6,6′-dimycolate (TDM), a major component of the mycobacterial cell wall, can elicit hypersensitive as well as T-cell-independent foreign body responses. The T-cell-independent contribution of TDM to the primary macrophage response to mycobacterial infection was investigated. Bone-marrow-derived macrophages isolated from C57BL/6 mice were infected with native (MTB) or with MTB delipidated using petroleum ether extraction methods. The removal of surface lipids caused decreased bacterial survival in macrophages, but there was no loss of bacterial growth in broth culture. Bacterial survival within macrophages was restored upon reconstitution of the bacteria with purified TDM. The cytokine and chemokine parameters of the macrophage responses were also investigated. The amounts of IL-1β, TNF-α, IL-6 and MIP-1α produced were significantly reduced following delipidation, but were restored upon reconstitution with TDM. The amount of IL-12 produced, but not the amount of IL-10 produced, was also significantly reduced upon macrophage infection with delipidated MTB. Furthermore, nitric oxide responses were not impaired upon infection with delipidated MTB, suggesting that intracellular survival and macrophage secretion of cytokines and chemokines are differentially controlled. These studies indicate that TDM is a major component contributing to the innate macrophage responses to MTB infection.

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2002-07-01
2024-03-28
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References

  1. Actor J. K., Olsen M., Jagannath C., Hunter R. L. 1999; Relationship of survival, organism containment, and granuloma formation in acute murine tuberculosis. J Interferon Cytokine Res 19:1183–1193 [CrossRef]
    [Google Scholar]
  2. Actor J. K., Leonard C. D., Watson V. E., Wells A., Jagannath C., Hunter R. L. Jr, Dasgupta A. 2000; Cytokine mRNA expression and serum cortisol evaluation during murine lung inflammation induced by Mycobacterium tuberculosis . Comb Chem High Throughput Screen 3:343–351
    [Google Scholar]
  3. Actor J. K., Breij E., Wetsel R. A., Hoffmann H., Hunter R. L. Jr, Jagannath C. 2001; A role for complement C5 in organism containment and granulomatous response during murine tuberculosis. Scand J Immunol 53:464–474 [CrossRef]
    [Google Scholar]
  4. Behling C. A., Perez R. L., Kidd M. R., Staton G. W. Jr, Hunter R. L. 1993; Induction of pulmonary granulomas, macrophage procoagulant activity, and tumor necrosis factor-alpha by trehalose glycolipids. Ann Clin Lab Sci 23:256–266
    [Google Scholar]
  5. Bloch H. 1950; Studies on the virulence of tubercle bacilli: isolation and biological properties of a constituent of virulent organisms. J Exp Med 91:197–217 [CrossRef]
    [Google Scholar]
  6. Chatterjee D., Roberts A. D., Lowell K., Brennan P. J., Orme I. M. 1992; Structural basis of capacity of lipoarabinomannan to induce secretion of tumor necrosis factor. Infect Immun 60:1249–1253
    [Google Scholar]
  7. Cooper A. M., Roberts A. D., Rhoades E. R., Callahan J. E., Getzy D. M., Orme I. M. 1995; The role of interleukin-12 in acquired immunity to Mycobacterium tuberculosis infection. Immunology 84:423–432
    [Google Scholar]
  8. Cooper A. M., Magram J., Ferrante J., Orme I. M. 1997; Interleukin 12 (IL-12) is crucial to the development of protective immunity in mice intravenously infected with Mycobacterium tuberculosis . J Exp Med 186:39–45 [CrossRef]
    [Google Scholar]
  9. Dahl K. E., Shiratsuchi H., Hamilton B. D., Ellner J. J., Toossi Z. 1996; Selective induction of transforming growth factor beta in human monocytes by lipoarabinomannan of Mycobacterium tuberculosis . Infect Immun 64:399–405
    [Google Scholar]
  10. Falk L. A. 1994; Isolation of bone marrow-derived macrophages. In Current Protocols in Immunology pp 14.0.3–14.1.9 Edited by Coligan J. E., Kruisbeck A. M., Margulies D. H., Shevach E. M., Strober W. New York: Wiley;
    [Google Scholar]
  11. Garcia I., Guler R., Vesin D., Olleros M. L., Vassalli P., Chvatchko Y., Jacobs M., Ryffel B. 2000; Lethal Mycobacterium bovis Bacillus Calmette–Guerin infection in nitric oxide synthase 2-deficient mice: cell-mediated immunity requires nitric oxide synthase 2. Lab Invest 80:1385–1397 [CrossRef]
    [Google Scholar]
  12. Hamasaki N., Isowa K., Kamada K., Terano Y., Matsumoto T., Arakawa T., Kobayashi K., Yano I. 2000; In vivo administration of mycobacterial cord factor (trehalose 6,6′-dimycolate) can induce lung and liver granulomas and thymic atrophy in rabbits. Infect Immun 68:3704–3709 [CrossRef]
    [Google Scholar]
  13. Jagannath C., Hoffman H., Sepulveda E., Actor J. K., Wetsel R. A., Hunter R. L. 2000; Hypersusceptibility of A/J mice to tuberculosis is in part due to a deficiency of the fifth complement component (C5). Scand J Immunol 52:369–379 [CrossRef]
    [Google Scholar]
  14. Jarlier V., Nikaido H. 1994; Mycobacterial cell wall: structure and role in natural resistance to antibiotics. FEMS Microbiol Lett 123:11–18 [CrossRef]
    [Google Scholar]
  15. Kolattukudy P. E., Fernandes N. D., Azad A. K., Fitzmaurice A. M., Sirakova T. D. 1997; Biochemistry and molecular genetics of cell-wall lipid biosynthesis in mycobacteria. Mol Microbiol 24:263–270 [CrossRef]
    [Google Scholar]
  16. Ladel C. H., Blum C., Dreher A., Reifenberg K., Kopf M., Kaufmann S. H. 1997; Lethal tuberculosis in interleukin-6-deficient mice. Infect Immun 65:4843–4849
    [Google Scholar]
  17. Middlebrook G., Dubos R. J., Pierce C. 1947; Virulence and morphological characteristics of mammalian tubercle bacilli. J Exp Med 86:175–187 [CrossRef]
    [Google Scholar]
  18. Noll H., Bloch H., Asselineau J., Lederer E. 1956; The chemical structure of the cord factor of Mycobacterium tuberculosis . Biochim Biophys Acta 20:299–309 [CrossRef]
    [Google Scholar]
  19. Oswald I. P., Dozois C. M., Petit J. F., Lemaire G. 1997; Interleukin-12 synthesis is a required step in trehalose dimycolate-induced activation of mouse peritoneal macrophages. Infect Immun 65:1364–1369
    [Google Scholar]
  20. Oswald I. P., Dozois C. M., Fournout S., Petit J. F., Lemaire G. 1999; Tumor necrosis factor is required for the priming of peritoneal macrophages by trehalose dimycolate. Eur Cytokine Netw 10:533–540
    [Google Scholar]
  21. Perez R. L., Roman J., Staton G. W. Jr, Hunter R. L. 1994; Extravascular coagulation and fibrinolysis in murine lung inflammation induced by the mycobacterial cord factor trehalose-6,6′-dimycolate. Am J Respir Crit Care Med 149:510–518 [CrossRef]
    [Google Scholar]
  22. Perez R. L., Roman J., Roser S., Little C., Olsen M., Indrigo J., Hunter R. L., Actor J. K. 2000; Cytokine message and protein expression during lung granuloma formation and resolution induced by the mycobacterial cord factor trehalose-6,6′-dimycolate. J Interferon Cytokine Res 20:795–804 [CrossRef]
    [Google Scholar]
  23. Roach T. I., Barton C. H., Chatterjee D., Blackwell J. M. 1993; Macrophage activation: lipoarabinomannan from avirulent and virulent strains of Mycobacterium tuberculosis differentially induces the early genes c-fos, KC, JE, and tumor necrosis factor-alpha. J Immunol 150:1886–1896
    [Google Scholar]
  24. Seah G. T., Scott G. M., Rook G. A. 2000; Type 2 cytokine gene activation and its relationship to extent of disease in patients with tuberculosis. J Infect Dis 181:385–389 [CrossRef]
    [Google Scholar]
  25. Seder R. A. 1995; The role of IL-12 in the regulation of Th1 and Th2 differentiation. Res Immunol 146:473–476 [CrossRef]
    [Google Scholar]
  26. Silva C. L., Ekizlerian S. M., Fazioli R. A. 1985; Role of cord factor in the modulation of infection caused by mycobacteria. Am J Pathol 118:238–247
    [Google Scholar]
  27. Spargo B. J., Crowe L. M., Ioneda T., Beaman B. L., Crowe J. H. 1991; Cord factor (α,α-trehalose 6,6′-dimycolate) inhibits fusion between phospholipid vesicles. Proc Natl Acad Sci USA 88:737–740 [CrossRef]
    [Google Scholar]
  28. Sutterwala F. S., Noel G. J., Clynes R., Mosser D. M. 1997; Selective suppression of interleukin-12 induction after macrophage receptor ligation. J Exp Med 185:1977–1985 [CrossRef]
    [Google Scholar]
  29. VanHeyningen T. K., Collins H. L., Russell D. G. 1997; IL-6 produced by macrophages infected with Mycobacterium species suppresses T cell responses. J Immunol 158:330–337
    [Google Scholar]
  30. Watson V. E., Hill L. L., Owen-Schaub L. B., Davis D. W., McConkey D. J., Jagannath C., Hunter R. L. Jr, Actor J. K. 2000; Apoptosis in Mycobacterium tuberculosis infection in mice exhibiting varied immunopathology. J Pathol 190:211–220 [CrossRef]
    [Google Scholar]
  31. Yamagami H., Matsumoto T., Fujiwara N., Arakawa T., Kaneda K., Yano I., Kobayashi K. 2001; Trehalose 6,6′-dimycolate (cord factor) of Mycobacterium tuberculosis induces foreign-body- and hypersensitivity-type granulomas in mice. Infect Immun 69:810–815 [CrossRef]
    [Google Scholar]
  32. Yoshida A., Koide Y. 1997; Arabinofuranosyl-terminated and mannosylated lipoarabinomannans from Mycobacterium tuberculosis induce different levels of interleukin-12 expression in murine macrophages. Infect Immun 65:1953–1955
    [Google Scholar]
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