1887

Abstract

Treatment of mouse macrophages with picolinic acid (PA) and -interferon (IFN) led to the restriction of proliferation concomitant with the sequential acquisition of metabolic changes typical of apoptosis, mitochondrial depolarization, annexin V staining and caspase activation, over a period of up to 5 days. However, triggering of cell death by ATP, staurosporine or HO failed to affect mycobacterial viability. In contrast to untreated macrophages where extensive interactions between phagosomes and endosomes were observed, phagosomes from treated macrophages lost the ability to acquire endosomal dextran. -Acetylcysteine was able to revert both the anti-mycobacterial activity of treated macrophages as well as the block in phagosome–endosome interactions. The treatment, however, induced only a minor increase in the acquisition of lysosomal markers, namely Lamp-1, and did not increase to any great extent the acidification of the phagosomes. These data thus suggest that the anti-mycobacterial activity of PA and IFN depends on the interruption of intracellular vesicular trafficking, namely the blocking of acquisition of endosomal material by the microbe.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.26815-0
2004-05-01
2020-04-05
Loading full text...

Full text loading...

/deliver/fulltext/micro/150/5/mic1501507.html?itemId=/content/journal/micro/10.1099/mic.0.26815-0&mimeType=html&fmt=ahah

References

  1. Appelberg R.. 1994; Protective role of gamma interferon, tumor necrosis factor alpha and interleukin-6 in Mycobacterium tuberculosis and M. avium infections. Immunobiology191:520–525[CrossRef]
    [Google Scholar]
  2. Armstrong J. A., d'Arcy-Hart P.. 1971; Response of cultured macrophages to Mycobacterium tuberculosis, with observations on fusion of lysosomes with phagosomes. J Exp Med134:713–740[CrossRef]
    [Google Scholar]
  3. Blasi E., Mazzolla R., Pitzurra L., Barluzzi R., Bistoni F.. 1993; Protective effect of picolinic acid on mice intracerebrally infected with lethal doses of Candida albicans. Antimicrob Agents Chemother37:2422–2426[CrossRef]
    [Google Scholar]
  4. Burke F., Knowles R. G., East N., Balkwill F. R.. 1995; The role of indoleamine 2,3-dioxygenase in the anti-tumour activity of human interferon-gamma in vivo. Int J Cancer60:115–122[CrossRef]
    [Google Scholar]
  5. Clemens D. L., Horwitz M. A.. 1995; Characterization of the Mycobacterium tuberculosis phagosome and evidence that phagosomal maturation is inhibited. J Exp Med181:257–270[CrossRef]
    [Google Scholar]
  6. Clemens D. L., Horwitz M. A.. 1996; The Mycobacterium tuberculosis phagosome interacts with early endosomes and is accessible to exogenously administered transferrin. J Exp Med184:1349–1355[CrossRef]
    [Google Scholar]
  7. Crowle A. J., Dahl R., Ross E., May M. H.. 1991; Evidence that vesicles containing living, virulent Mycobacterium tuberculosis or Mycobacterium avium in cultured human macrophages are not acidic. Infect Immun59:1823–1831
    [Google Scholar]
  8. de Chastellier C., Thilo L.. 1997; Phagosome maturation and fusion with lysosomes in relation to endocytic membranes and size of the phagocytic particle. Eur J Cell Biol74:49–62
    [Google Scholar]
  9. de Chastellier C., Lang T., Thilo L.. 1995; Phagocytic processing of the macrophage endoparasite, Mycobacterium avium, in comparison to phagosomes which contain Bacillus subtilis or latex beads. Eur J Cell Biol68:167–182
    [Google Scholar]
  10. de Chastellier C., Thibon M., Rabinovitch M.. 1999; Construction of chimeric phagosomes that shelter Mycobacterium avium and Coxiella burnetii (phase II) in doubly infected mouse macrophages: an ultrastructural study. Eur J Cell Biol78:580–592[CrossRef]
    [Google Scholar]
  11. Fairbairn I. P., Stober C. B., Kumararatne D. S., Lammas D. A.. 2001; ATP-mediated killing of intracellular mycobacteria by macrophages is a P2X(7)-dependent process inducing bacterial death by phagosome–lysosome fusion. J Immunol167:3300–3307[CrossRef]
    [Google Scholar]
  12. Falkinham J. O. III. 1996; Epidemiology of infection by nontuberculous mycobacteria. Clin Microbiol Rev9:177–215
    [Google Scholar]
  13. Ferrari G., Langen H., Naito M., Pieters J.. 1999; A coat protein on phagosomes involved in the intracellular survival of mycobacteria. Cell97:435–447[CrossRef]
    [Google Scholar]
  14. Fratti R. A., Chua J., Vergne I., Deretic V.. 2003; Mycobacterium tuberculosis glycosylated phosphatidylinositol causes phagosome maturation arrest. Proc Natl Acad Sci U S A100:5437–5442[CrossRef]
    [Google Scholar]
  15. Frehel C., de Chastellier C., Lang T., Rastogi N.. 1986; Evidence for inhibition of fusion of lysosomal and prelysosomal compartments with phagosomes in macrophages infected with pathogenic Mycobacterium avium. Infect Immun52:252–262
    [Google Scholar]
  16. Fuchs D., Forsman A., Hagberg L., Larsson M., Norkrans G., Reibnegger G., Werner E. R., Wachter H.. 1990; Immune activation and decreased tryptophan in patients with HIV-1 infection. J Interferon Res10:599–603[CrossRef]
    [Google Scholar]
  17. Gomes M. S., Appelberg R.. 2002; Nramp1- or cytokine-induced bacteriostasis of Mycobacterium avium by mouse macrophages is independent of the respiratory burst. Microbiology148:3155–3160
    [Google Scholar]
  18. Gomes M. S., Flórido M., Pais T. F., Appelberg R.. 1999a; Improved clearance of Mycobacterium avium upon disruption of the iNOS gene. J Immunol162:6734–6739
    [Google Scholar]
  19. Gomes M. S., Paul S., Moreira A. L., Appelberg R., Rabinovitch M., Kaplan G.. 1999b; Survival of Mycobacterium avium and Mycobacterium tuberculosis in acidified vacuoles of murine macrophages. Infect Immun67:3199–3206
    [Google Scholar]
  20. Guérin I., de Chastellier C.. 2000; Disruption of the actin filament network affects delivery of endocytic contents marker to phagosomes with early endosome characteristics: the case of phagosomes with pathogenic mycobacteria. Eur J Cell Biol79:735–749[CrossRef]
    [Google Scholar]
  21. Heinzen R. A., Scidmore M. A., Rockey D. D., Hackstadt T.. 1996; Differential interaction with endocytic and exocytic pathways distinguish parasitophorous vacuoles of Coxiella burnetti and Chlamydia trachomatis. Infect Immun64:796–809
    [Google Scholar]
  22. Holland S. M.. 1996; Host defense against nontuberculous mycobacterial infections. Semin Respir Infect11:217–230
    [Google Scholar]
  23. Kusner D. J., Adams J.. 2000; ATP-induced killing of virulent Mycobacterium tuberculosis within human macrophages requires phospholipase D. J Immunol164:379–388[CrossRef]
    [Google Scholar]
  24. Kusner D. J., Barton J. A.. 2001; ATP stimulates human macrophages to kill intracellular virulent Mycobacterium tuberculosis via calcium-dependent phagosome–lysosome fusion. J Immunol167:3308–3315[CrossRef]
    [Google Scholar]
  25. Lammas D. A., Stober C., Harvey C. J., Kendrick N., Panchalingam S., Kumararatne D. S.. 1997; ATP-induced killing of mycobacteria by human macrophages is mediated by purinergic P2Z(P2X7) receptors. Immunity7:433–444[CrossRef]
    [Google Scholar]
  26. Laochumroonvorapong P., Paul S., Elkon K. B., Kaplan G.. 1996; H2O2 induces monocyte apoptosis and reduces viability of Mycobacterium avium-M. intracellulare within cultured human monocytes. Infect Immun64:452–459
    [Google Scholar]
  27. Leuthauser S. W. C., Oberley L. W., Oberley T. D.. 1982; Antitumor activity of picolinic acid in CBA/J mice. J Natl Cancer Inst68:123–126
    [Google Scholar]
  28. Macen J., Takahashi A., Moon K. B., Nathaniel R., Turner P. C., Moyer R. W.. 1998; Activation of caspases in pig kidney cells infected with wild-type and CrmA/SPI-2 mutants of cowpox and rabbitpox viruses. J Virol72:3524–3533
    [Google Scholar]
  29. Malik Z. A., Iyer S. S., Kusner D. J.. 2001; Mycobacterium tuberculosis phagosomes exhibit altered calmodulin-dependent signal transduction: contribution to inhibition of phagosome–lysosome fusion and intracellular survival in human macrophages. J Immunol166:3392–3401[CrossRef]
    [Google Scholar]
  30. Medana I. M., Day N. P., Salahifar-Sabet H.. & 8 other authors. 2003; Metabolites of the kynurenine pathway of tryptophan metabolism in the cerebrospinal fluid of Malawian children with malaria. J Infect Dis188:844–849[CrossRef]
    [Google Scholar]
  31. Molloy A., Laochumroonvorapong P., Kaplan G.. 1994; Apoptosis, but not necrosis, of infected monocytes is coupled with killing of intracellular bacillus Calmette-Guerin. J Exp Med180:1499–1509[CrossRef]
    [Google Scholar]
  32. Oddo M., Renno T., Attinger A., Bakker T., MacDonald H. R., Meylan P. R.. 1998; Fas ligand-induced apoptosis of infected human macrophages reduces the viability of intracellular Mycobacterium tuberculosis. J Immunol160:5448–5454
    [Google Scholar]
  33. Ojcius D. M., Niedergang F., Subtil A., Hellio R., Dautry-Varsat A.. 1996; Immunology and the confocal microscope. Res Immunol147:175–188[CrossRef]
    [Google Scholar]
  34. Pais T. F., Appelberg R.. 2000; Macrophage control of mycobacterial growth induced by picolinic acid is dependent on host cell apoptosis. J Immunol164:389–397[CrossRef]
    [Google Scholar]
  35. Parlato S., Giammarioli A. M., Logozzi M., Lozupone F., Matarrese P., Luciani F., Falchi M., Malorni W., Fais S.. 2000; CD95 (APO-1/Fas) linkage to the actin cytoskeleton through ezrin in human T lymphocytes: a novel regulatory mechanism of the CD95 apoptotic pathway. EMBO J19:5123–5134[CrossRef]
    [Google Scholar]
  36. Polla B. S., Kantengwa S., Francois D., Salvioli S., Franceschi C., Marsac C., Cossarizza A.. 1996; Mitochondria are selective targets for the protective effects of heat shock against oxidative injury. Proc Natl Acad Sci U S A93:6458–6463[CrossRef]
    [Google Scholar]
  37. Ruffmann R., Welker R. D., Saito T., Chirigos M. A., Varesio L.. 1984; In vivo activation of macrophages but not natural killer cells by picolinic acid (PLA. J Immunopharmacol6:291–304[CrossRef]
    [Google Scholar]
  38. Russell D. G., Dant J., Sturgill-Koszycki S.. 1996; Mycobacterium avium- and Mycobacterium tuberculosis-containing vacuoles are dynamic, fusion-competent vesicles that are accessible to glycosphingolipids from the host cell plasmalemma. J Immunol156:4764–4773
    [Google Scholar]
  39. Russell D. G., Sturgill-Koszycki S., Vanheyningen T., Collins H., Schaible U. E.. 1997; Why intracellular parasitism need not be a degrading experience for Mycobacterium. Philos Trans R Soc Lond B Biol Sci352:1303–1310[CrossRef]
    [Google Scholar]
  40. Schaible U. E., Sturgill-Koszycki S., Schlesinger P. H., Russell D. G.. 1998; Cytokine activation leads to acidification and increases maturation of Mycobacterium avium-containing phagosomes in murine macrophages. J Immunol160:1290–1296
    [Google Scholar]
  41. Schuller S., Neefjes J., Ottenhoff T., Thole J., Young D.. 2001; Coronin is involved in uptake of Mycobacterium bovis BCG in human macrophages but not in phagosome maintenance. Cell Microbiol3:785–793[CrossRef]
    [Google Scholar]
  42. Smiley S. T., Reers M., Mottola-Hartshorn C., Lin M., Chen A., Smith T. W., Steele G. D. Jr, Chen L. B.. 1991; Intracellular heterogeneity in mitochondrial membrane potentials revealed by a J-aggregate-forming lipophilic cation JC-1. Proc Natl Acad Sci U S A88:3671–3675[CrossRef]
    [Google Scholar]
  43. Stober C. B., Lammas D. A., Li C. M., Kumararatne D. S., Lightman S. L., McArdle C. A.. 2001; ATP-mediated killing of Mycobacterium bovis bacille Calmette-Guerin within human macrophages is calcium dependent and associated with the acidification of mycobacteria-containing phagosomes. J Immunol166:6276–6286[CrossRef]
    [Google Scholar]
  44. Sturgill-Koszycki S., Schlesinger P. H., Chakraborty P.. & 7 other authors. 1994; Lack of acidification in Mycobacterium phagosomes produced by exclusion of the vesicular proton-ATPase. Science263:678–681[CrossRef]
    [Google Scholar]
  45. Sturgill-Koszycki S., Schaible U. E., Russell D. G.. 1996; Mycobacterium-containing phagosomes are accessible to early endosomes and reflect a transitional state in normal phagosome biogenesis. EMBO J15:6960–6968
    [Google Scholar]
  46. Varesio L., Clayton M., Blasi E., Ruffman R., Raadzioch D.. 1990; Picolinic acid, a catabolite of tryptophan, as the second signal in the activation of IFNγ-primed macrophages. J Immunol145:4265–4271
    [Google Scholar]
  47. Via L. E., Deretic D., Ulmer R. J., Hibler N. S., Huber L. A., Deretic V.. 1997; Arrest of mycobacterial phagosome maturation is caused by a block in vesicle fusion between stages controlled by rab5 and rab7. J Biol Chem272:13326–13331[CrossRef]
    [Google Scholar]
  48. Wannemacher R. W.. 1977; Key role of various individual amino acids in host response to infection. J Clin Nutr30:1269–1280
    [Google Scholar]
  49. Xu S., Cooper A., Sturgill-Koszycki S., van Heyningen T., Chatterjee D., Orme I., Allen P., Russell D. G.. 1994; Intracellular trafficking in Mycobacterium tuberculosis and Mycobacterium avium-infected macrophages. J Immunol153:2568–2578
    [Google Scholar]
  50. Zamzami N., Marchetti P., Castedo M.. & 7 other authors. 1995; Sequential reduction of mitochondrial transmembrane potential and generation of reactive oxygen species in early programmed cell death. J Exp Med182:367–377[CrossRef]
    [Google Scholar]
  51. Zingarelli B., O'Connor M., Wong H., Salzman A. L., Szabo C.. 1996; Peroxynitrite-mediated DNA strand breakage activates poly-adenosine diphosphate ribosyl synthetase and causes cellular energy depletion in macrophages stimulated with bacterial lipopolysaccharide. J Immunol156:350–358
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.26815-0
Loading
/content/journal/micro/10.1099/mic.0.26815-0
Loading

Data & Media loading...

Most cited this month

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