1887

Abstract

The granulomatous response is the characteristic histological feature of infection that is essential for organism containment. Trehalose 6,6-dimycolate (TDM), a cell-wall glycolipid present on most mycobacterial species, has been implicated in the pathogenesis of infection. TDM has potent immunoregulatory and inflammatory properties, and can be used to model granulomatous reactions that mimic, in part, pathology caused during active infection. This study examined the hypersensitive granulomatous response, focusing on cellular responses specific to TDM. Lungs from mice immunized with TDM emulsion demonstrated exacerbated histological damage, inflammation, and lymphocytic infiltration upon subsequent challenge with TDM. Splenocytes recovered from these mice demonstrated significant interferon (IFN)- production during recall response to TDM, as well as increased production of proinflammatory mediators (tumour necrosis factor-, interleukin-6 and macrophage inflammatory protein-1). The exacerbated response could be adoptively transferred to naïve mice. Administration of non-adherent lymphocytes or purified CD3 cells from TDM-immunized mice led to increased inflammation, lymphocytic infiltration, and vascular endothelial cell damage upon challenge with TDM. Recipient mice that received immunized CD3 lymphocytes demonstrated significant increases in Th1-type cytokines and proinflammatory mediators in lung tissue following TDM challenge. When CD1d mice were immunized with TDM, they failed to generate a specific IFN- response, suggesting a role for this molecule in the generation of hypersensitivity. These experiments provide further evidence for the involvement of TDM-specific CD3 T cells in pathological damage elicited during infection.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.29290-0
2006-12-01
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/micro/152/12/3765.html?itemId=/content/journal/micro/10.1099/mic.0.29290-0&mimeType=html&fmt=ahah

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, Olsen M, Geng Y. J, Hunter R. L Jr. 2001; Dysregulated response to mycobacterial cord factor trehalose-6,6′-dimycolate in CD1D-/- mice. J Interferon Cytokine Res 21:1089–1096 [CrossRef]
    [Google Scholar]
  3. Actor J. K, Indrigo J, Beachdel C. M, Olsen M, Wells A, Dasgupta A, Hunter R. L Jr. 2002; Mycobacterial glycolipid cord factor trehalose 6,6′-dimycolate causes a decrease in serum cortisol during the granulomatous response. Neuroimmunomodulation 10:270–282 [CrossRef]
    [Google Scholar]
  4. Algood H. M, Chan J, Flynn J. L. 2003; Chemokines and tuberculosis. Cytokine Growth Factor Rev 14:467–477 [CrossRef]
    [Google Scholar]
  5. Behar S. M, Dascher C. C, Grusby M. J, Wang C. R, Brenner M. B. 1999; Susceptibility of mice deficient in CD1D or TAP1 to infection with Mycobacterium tuberculosis . J Exp Med 189:1973–1980 [CrossRef]
    [Google Scholar]
  6. Behling C. A, Perez R. L, Kidd M. R, Hunter R. L, Staton G. W Jr. 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]
  7. Bekierkunst A. 1968; Acute granulomatous response produced in mice by trehalose-6,6-dimycolate. J Bacteriol 96:958–961
    [Google Scholar]
  8. Bekierkunst A, Yarkoni E. 1973; Granulomatous hypersensitivity to trehalose-6,6′-dimycolate (cord factor) in mice infected with BCG. Infect Immun 7:631–638
    [Google Scholar]
  9. Belisle J. T, Vissa V. D, Sievert T, Takayama K, Brennan P. J, Besra G. S. 1997; Role of the major antigen of Mycobacterium tuberculosis in cell wall biogenesis. Science 276:1420–1422 [CrossRef]
    [Google Scholar]
  10. Bloch H. 1950; Studies on the virulence of tubercle bacilli; the relationship of the physiological state of the organisms to their pathogenicity. J Exp Med 92:507–526 [CrossRef]
    [Google Scholar]
  11. Borders C. W, Courtney A, Ronen K. 8 other authors 2005; Requisite role for complement C5 and the C5a receptor in granulomatous response to mycobacterial glycolipid trehalose 6,6′-dimycolate. Scand J Immunol 62:123–130 [CrossRef]
    [Google Scholar]
  12. Brennan P. J. 2003; Structure, function, and biogenesis of the cell wall of Mycobacterium tuberculosis . Tuberculosis 83:91–97 [CrossRef]
    [Google Scholar]
  13. Collins F. M, Congdon C. C, Morrison N. E. 1975; Growth of mycobacterium bovis (BCG) in T lymphocyte-depleted mice. Infect Immun 11:57–64
    [Google Scholar]
  14. Cooper A. M, Dalton D. K, Stewart T. A, Griffin J. P, Russell D. G, Orme I. M. 1993; Disseminated tuberculosis in interferon gamma gene-disrupted mice. J Exp Med 178:2243–2247 [CrossRef]
    [Google Scholar]
  15. Dannenberg A. M Jr. 1991; Delayed-type hypersensitivity and cell-mediated immunity in the pathogenesis of tuberculosis. Immunol Today 12:228–233 [CrossRef]
    [Google Scholar]
  16. Dimakou K, Papaioannides D, Latsi P, Katsimboula S, Korantzopoulos P, Orphanidou D. 2004; Disseminated tuberculosis complicating anti-TNF-alpha treatment. Int J Clin Pract 58:1052–1055 [CrossRef]
    [Google Scholar]
  17. Dubnau E, Chan J, Raynaud C, Mohan V. P, Laneelle M. A, Yu K, Quemard A, Smith I, Daffe M. 2000; Oxygenated mycolic acids are necessary for virulence of Mycobacterium tuberculosis in mice. Mol Microbiol 36:630–637
    [Google Scholar]
  18. Geisel R. E, Sakamoto K, Russell D. G, Rhoades E. R. 2005; In vivo activity of released cell wall lipids of Mycobacterium bovis bacillus Calmette-Guerin is due principally to trehalose mycolates. J Immunol 174:5007–5015 [CrossRef]
    [Google Scholar]
  19. Glickman M. S, Cox J. S, Jacobs W. R Jr. 2000; A novel mycolic acid cyclopropane synthetase is required for cording, persistence, and virulence of Mycobacterium tuberculosis . Mol Cell 5:717–727 [CrossRef]
    [Google Scholar]
  20. Gomez-Reino J. J, Carmona L, Valverde V. R, Mola E. M, Montero M. D. 2003; Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: a multicenter active-surveillance report. Arthritis Rheum 48:2122–2127 [CrossRef]
    [Google Scholar]
  21. Guidry T. V, Olsen M, Kil K. S, Geng Y. J, Actor J. K, Hunter R. L Jr. 2004; Failure of CD1D-/- mice to elicit hypersensitive granulomas to mycobacterial cord factor trehalose 6,6′-dimycolate. J Interferon Cytokine Res 24:362–371 [CrossRef]
    [Google Scholar]
  22. Hahn H, Kaufmann S. H. 1981; The role of cell-mediated immunity in bacterial infections. Rev Infect Dis 3:1221–1250 [CrossRef]
    [Google Scholar]
  23. Holten-Andersen L, Doherty T. M, Korsholm K. S, Andersen P. 2004; Combination of the cationic surfactant dimethyl dioctadecyl ammonium bromide and synthetic mycobacterial cord factor as an efficient adjuvant for tuberculosis subunit vaccines. Infect Immun 72:1608–1617 [CrossRef]
    [Google Scholar]
  24. Hunter R. L, Olsen M, Jagannath C, Actor J. K. 2006; Trehalose 6,6′-dimycolate and lipid in the pathogenesis of caseating granulomas of tuberculosis in mice. Am J Pathol 168:1249–1261 [CrossRef]
    [Google Scholar]
  25. Hussein S, Curtis J, Akuffo H, Turk J. L. 1987; Dissociation between delayed-type hypersensitivity and resistance to pathogenic mycobacteria demonstrated by T-cell clones. Infect Immun 55:564–567
    [Google Scholar]
  26. Indrigo J, Actor J. K, Hunter R. L Jr. 2002; Influence of trehalose 6,6′-dimycolate (TDM) during mycobacterial infection of bone marrow macrophages. Microbiology 148:1991–1998
    [Google Scholar]
  27. Indrigo J, Actor J. K, Hunter R. L Jr. 2003; Cord factor trehalose 6,6′-dimycolate (TDM) mediates trafficking events during mycobacterial infection of murine macrophages. Microbiology 149:2049–2059 [CrossRef]
    [Google Scholar]
  28. Karakousis P. C, Bishai W. R, Dorman S. E. 2004; Mycobacterium tuberculosis cell envelope lipids and the host immune response. Cell Microbiol 6:105–116 [CrossRef]
    [Google Scholar]
  29. Lima V. M, Bonato V. L, Lima K. M. 7 other authors 2001; Role of trehalose dimycolate in recruitment of cells and modulation of production of cytokines and NO in tuberculosis. Infect Immun 69:5305–5312 [CrossRef]
    [Google Scholar]
  30. 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]
  31. Oiso R, Fujiwara N, Yamagami H. 7 other authors 2005; Mycobacterial trehalose 6,6′-dimycolate preferentially induces type 1 helper T cell responses through signal transducer and activator of transcription 4 protein. Microb Pathog 39:35–43 [CrossRef]
    [Google Scholar]
  32. 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]
  33. 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]
  34. 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]
  35. Pimm M. V, Baldwin R. W, Polonsky J, Lederer E. 1979; Immunotherapy of an ascitic rat hepatoma with cord factor (trehalose-6, 6′-dimycolate) and synthetic analogues. Int J Cancer 24:780–785 [CrossRef]
    [Google Scholar]
  36. Rao V, Fujiwara N, Porcelli S. A, Glickman M. S. 2005; Mycobacterium tuberculosis controls host innate immune activation through cyclopropane modification of a glycolipid effector molecule. J Exp Med 201:535–543 [CrossRef]
    [Google Scholar]
  37. Rao V, Gao F, Chen B, Glickman M. S, Jacobs W. R Jr. 2006; Trans-cyclopropanation of mycolic acids on trehalose dimycolate suppresses Mycobacterium tuberculosis -induced inflammation and virulence. J Clin Invest 116:1660–1667 [CrossRef]
    [Google Scholar]
  38. Reggiardo Z, Middlebrook G. 1974; Delayed-type hypersensitivity and immunity against aerogenic tuberculosis in guinea pigs. Infect Immun 9:815–820
    [Google Scholar]
  39. Retzinger G. S, Meredith S. C, Takayama K, Hunter R. L, Kezdy F. J. 1981; The role of surface in the biological activities of trehalose 6,6′-dimycolate. Surface properties and development of a model system. J Biol Chem 256:8208–8216
    [Google Scholar]
  40. Roach D. R, Bean A. G, Demangel C, France M. P, Briscoe H, Britton W. J. 2002; TNF regulates chemokine induction essential for cell recruitment, granuloma formation, and clearance of mycobacterial infection. J Immunol 168:4620–4627 [CrossRef]
    [Google Scholar]
  41. Rook G. A. 1978; Three forms of delayed skin-test response evoked by mycobacteria. Nature 271:64–65 [CrossRef]
    [Google Scholar]
  42. Ryll R, Watanabe K, Fujiwara N, Takimoto H, Hasunuma R, Kumazawa Y, Okada M, Yano I. 2001; Mycobacterial cord factor, but not sulfolipid, causes depletion of NKT cells and upregulation of CD1d1 on murine macrophages. Microbes Infect 3:611–619 [CrossRef]
    [Google Scholar]
  43. Sayers I, Severn W, Scanga C. B, Hudson J, Le Gros G, Harper J. L. 2004; Suppression of allergic airway disease using mycobacterial lipoglycans. J Allergy Clin Immunol 114:302–309 [CrossRef]
    [Google Scholar]
  44. Scanga C. A, Mohan V. P, Yu K, Joseph H, Tanaka K, Chan J, Flynn J. L. 2000; Depletion of CD4(+) T cells causes reactivation of murine persistent tuberculosis despite continued expression of interferon gamma and nitric oxide synthase 2. J Exp Med 192:347–358 [CrossRef]
    [Google Scholar]
  45. Schroeder E. K, Santos D. S, Blanchard J. S, Basso L. A, de Souza N. 2002; Drugs that inhibit mycolic acid biosynthesis in Mycobacterium tuberculosis . Curr Pharm Biotechnol 3:197–225 [CrossRef]
    [Google Scholar]
  46. Seggev J, Goren M. B, Carr R. I, Kirkpatrick C. H. 1982; Interstitial and hemorrhagic pneumonitis induced by mycobacterial trehalose dimycolate. Am J Pathol 106:348–355
    [Google Scholar]
  47. Seggev J. S, Goren M. B, Kirkpatrick C. H. 1984; The pathogenesis of trehalose dimycolate-induced interstitial pneumonitis. III. Evidence for a role for T lymphocytes. Cell Immunol 85:428–435 [CrossRef]
    [Google Scholar]
  48. 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]
  49. Skold M, Behar S. M. 2005; The role of group 1 and group 2 CD1-restricted T cells in microbial immunity. Microbes Infect 7:544–551 [CrossRef]
    [Google Scholar]
  50. Skold M, Xiong X, Illarionov P. A, Besra G. S, Behar S. M. 2005; Interplay of cytokines and microbial signals in regulation of CD1d expression and NKT cell activation. J Immunol 175:3584–3593 [CrossRef]
    [Google Scholar]
  51. Spargo B. J, Crowe L. M, Ioneda T, Beaman B. L, Crowe J. H. 1991; Cord factor (alpha,alpha-trehalose 6,6′-dimycolate) inhibits fusion between phospholipid vesicles. Proc Natl Acad Sci U S A 88:737–740 [CrossRef]
    [Google Scholar]
  52. Szalay G, Zugel U, Ladel C. H, Kaufmann S. H. 1999; Participation of group 2 CD1 molecules in the control of murine tuberculosis. Microbes Infect 1:1153–1157 [CrossRef]
    [Google Scholar]
  53. Takimoto H, Maruyama H, Shimada K. I, Yakabe R, Yano I, Kumazawa Y. 2006; Interferon-gamma independent formation of pulmonary granuloma in mice by injections with trehalose dimycolate (cord factor), lipoarabinomannan and phosphatidylinositol mannosides isolated from Mycobacterium tuberculosis . Clin Exp Immunol 144:134–141 [CrossRef]
    [Google Scholar]
  54. 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]
  55. Yarkoni E, Rapp H. J. 1978; Toxicity of emulsified trehalose-6,6′-dimycolate (cord factor) in mice depends on size distribution of mineral oil droplets. Infect Immun 20:856–860
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.29290-0
Loading
/content/journal/micro/10.1099/mic.0.29290-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error