1887

Abstract

The entry of () into the host macrophage and its survival in this environment are key components of tuberculosis pathogenesis. Following intracellular replication of the bacterium within alveolar macrophages, there is spread of bacilli to regional lymph nodes in the lungs and subsequent presentation of antigens to the host immune system. How this process occurs remains poorly understood, but one mechanism may involve the migration of macrophages containing across the alveoli to lymph nodes, where there is development of a protective host response with formation of granulomas composed in part of aggregated and fused, apoptotic, infected macrophages. Leukocyte integrins, including lymphocyte function-associated antigen-1 (LFA-1) and complement receptors CR3 and CR4, and their counter receptors play a major role in macrophage adhesion processes and phagocytosis. In this study, the appearance of -infected macrophages over time was examined, using inverted-phase microscopy and an culture model of human monocyte-derived macrophages (MDMs). Prior to and immediately following infection of the MDMs with , the macrophages appeared as individual cells in monolayer culture; however, within 24 h of infection with , the MDMs began to migrate and adhere to each other. The kinetics of this response were dependent on both the m.o.i. and the length of infection. Quantitative transmission electron microscopy studies revealed that macrophage adhesion was accompanied by increases in levels of LFA-1 and its counter receptor (ICAM-1), decreases in surface levels of the phagocytic receptors CR3, CR4 and FcγRII, and an increase in major histocompatibility complex Class II (MHC-II) molecules at 72 h post-infection. Decreases in surface levels of CR3 and CR4 had a functional correlate, with macrophages containing live bacilli showing a diminished phagocytic capacity for complement-opsonized sheep erythrocytes; macrophages containing heat-killed bacilli did not show this diminished capacity. The modulation of macrophage adhesion and phagocytic proteins may influence the trafficking of -infected macrophages within the host, with increases in levels of LFA-1 and ICAM-1 enhancing the adhesive properties of the macrophage and decreases in phagocytic receptors diminishing the phagocytic capacity of an already-infected cell, potentially allowing for maintenance of the intracellular niche of

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2002-10-01
2019-10-15
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References

  1. Bellingan, G. J., Caldwell, H., Howie, S. E. M., Dransfield, I. & Haslett, C. ( 1996; ). In vivo fate of the inflammatory macrophage during the resolution of inflammation: inflammatory macrophages do not die locally, but emigrate to the draining lymph nodes. J Immunol 157, 2577-2585.
    [Google Scholar]
  2. Blackford, J., Reid, H. W., Pappin, D. J. C., Bowers, F. S. & Wilkinson, J. M. ( 1996; ). A monoclonal antibody, 3/22, to rabbit CD11c which induces homotypic T cell aggregation: evidence that ICAM-1 is a ligand for CD11c/CD18. Eur J Immunol 26, 525-531.[CrossRef]
    [Google Scholar]
  3. Demangel, C., Bean, A. G., Martin, E., Feng, C. G., Kamath, A. T. & Britton, W. J. ( 1999; ). Protection against aerosol Mycobacterium tuberculosis infection using Mycobacterium bovis Bacillus Calmette Guerin-infected dendritic cells. Eur J Immunol 29, 1972-1979.[CrossRef]
    [Google Scholar]
  4. Dubey, C. & Croft, M. ( 1996; ). Accessory molecule regulation of naive CD4 T cell activation. Immunol Res 15, 114-125.[CrossRef]
    [Google Scholar]
  5. Ehrt, S., Schnappinger, D., Bekiranov, S., Drenkow, J., Shi, S., Gingeras, T. R., Gaasterland, T., Schoolnik, G. & Nathan, C. ( 2001; ). Reprogramming of the macrophage transcriptome in response to interferon-gamma and Mycobacterium tuberculosis: signaling roles of nitric oxide synthase-2 and phagocyte oxidase. J Exp Med 194, 1123-1140.[CrossRef]
    [Google Scholar]
  6. Ezekowitz, R. A. B., Austyn, J., Stahl, P. D. & Gordon, S. ( 1981; ). Surface properties of bacillus Calmette–Guerin-activated mouse macrophages. Reduced expression of mannose-specific endocytosis, Fc receptors, and antigen F4/80 accompanies induction of Ia. J Exp Med 154, 60-76.[CrossRef]
    [Google Scholar]
  7. Faull, R. J., Kovach, N. L., Harlan, J. M. & Ginsberg, M. H. ( 1994; ). Stimulation of integrin-mediated adhesion of T lymphocytes and monocytes: two mechanisms with divergent biological consequences. J Exp Med 179, 1307-1316.[CrossRef]
    [Google Scholar]
  8. Fenton, M. J. ( 1998; ). Macrophages and tuberculosis. Curr Opin Hematol 5, 72-78.[CrossRef]
    [Google Scholar]
  9. Ferguson, J. S., Voelker, D. R., Ufnar, J. A. & Schlesinger, L. S. ( 2002; ). Surfactant protein D inhibition of human macrophage uptake of Mycobacterium tuberculosis is independent of bacterial agglutination. J Immunol 168, 1309-1314.[CrossRef]
    [Google Scholar]
  10. Fratazzi, C., Arbeit, R. D., Carini, C., Balcewicz-Sablinska, M. K., Keane, J., Kornfeld, H. & Remold, H. C. ( 1999; ). Macrophage apoptosis in mycobacterial infections. J Leukoc Biol 66, 763-764.
    [Google Scholar]
  11. Gercken, J., Pryjma, J., Ernst, M. & Flad, H.-D. ( 1994; ). Defective antigen presentation by Mycobacterium tuberculosis-infected monocytes. Infect Immun 62, 3472-3478.
    [Google Scholar]
  12. Hamerman, J. A. & Aderem, A. ( 2001; ). Functional transitions in macrophages during in vivo infection with Mycobacterium bovis bacillus Calmette–Guérin. J Immunol 167, 2227-2233.[CrossRef]
    [Google Scholar]
  13. Harmsen, A. G., Muggenburg, B. A., Snipes, M. B. & Bice, D. E. ( 1985; ). The role of macrophages in particle translocation from lungs to lymph nodes. Science 230, 1277-1280.[CrossRef]
    [Google Scholar]
  14. Harris, E. S., McIntyre, T. M., Prescott, S. M. & Zimmerman, G. A. ( 2000; ). The leukocyte integrins. J Biol Chem 275, 23409-23412.[CrossRef]
    [Google Scholar]
  15. Herscowitz, H. B. ( 1985; ). In defense of the lung: paradoxical role of the pulmonary alveolar macrophage. Ann Allergy 55, 634-650.
    [Google Scholar]
  16. Hirsch, C. S., Ellner, J. J., Russell, D. G. & Rich, E. A. ( 1994; ). Complement receptor-mediated uptake and tumor necrosis factor-alpha-mediated growth inhibition of Mycobacterium tuberculosis by human alveolar macrophages. J Immunol 152, 743-753.
    [Google Scholar]
  17. Hmama, Z., Gabathuler, R., Jefferies, W. A., de Jong, G. & Reiner, N. E. ( 1998; ). Attenuation of HLA-DR expression by mononuclear phagocytes infected with Mycobacterium tuberculosis is related to intracellular sequestration of immature class II heterodimers. J Immunol 161, 4882-4893.
    [Google Scholar]
  18. Ingalls, R. R. & Golenbock, D. T. ( 1995; ). CD11c/CD18, a transmembrane signaling receptor for lipopolysaccharide. J Exp Med 181, 1473-1479.[CrossRef]
    [Google Scholar]
  19. Kaye, P. M., Sims, M. & Feldmann, M. ( 1986; ). Regulation of macrophage accessory cell activity by mycobacteria. II. In vitro inhibition of Ia expression by Mycobacterium microti. Clin Exp Immunol 64, 28-34.
    [Google Scholar]
  20. Keane, J., Balcewicz-Sablinska, M. K., Remold, H. G., Chupp, G. L., Meek, B. B., Fenton, M. J. & Kornfeld, H. ( 1997; ). Infection by Mycobacterium tuberculosis promotes human alveolar macrophage apoptosis. Infect Immun 65, 298-304.
    [Google Scholar]
  21. Keller, R., Keist, R. & Joller, P. ( 1995; ). Macrophage response to microbial pathogens: modulation of the expression of adhesion, CD14, and MHC class II molecules by viruses, bacteria, protozoa and fungi. Scand J Immunol 42, 337-344.[CrossRef]
    [Google Scholar]
  22. Lambrecht, B. N., Prins, J.-B. & Hoogsteden, H. C. ( 2001; ). Lung dendritic cells and host immunity to infection. Eur Respir J 18, 692-704.
    [Google Scholar]
  23. Loike, J. D., Sodeik, B., Cao, L., Leucona, S., Weitz, J. I., Detmers, P. A., Wright, S. D. & Silverstein, S. C. ( 1991; ). CD11c/CD18 on neutrophils recognizes a domain at the N terminus of the Aα chain of fibrinogen. Proc Natl Acad Sci USA 88, 1044-1048.[CrossRef]
    [Google Scholar]
  24. López Ramı́rez, G. M., Rom, W. N., Ciotoli, C., Talbot, A., Martiniuk, F., Cronstein, B. & Reibman, J. ( 1994; ). Mycobacterium tuberculosis alters expression of adhesion molecules on monocytic cells. Infect Immun 62, 2515-2520.
    [Google Scholar]
  25. Mariano, M., Nikitin, T. & Malucelli, B. E. ( 1977; ). Phagocytic potential of macrophages from within delayed hypersensitivity-mediated granulomata. J Pathol 123, 27-33.[CrossRef]
    [Google Scholar]
  26. McDonough, K. A. & Kress, Y. ( 1995; ). Cytotoxicity for lung epithelial cells is a virulence-associated phenotype of Mycobacterium tuberculosis. Infect Immun 63, 4802-4811.
    [Google Scholar]
  27. Mohagheghpour, N., Gammon, D., van Vollenhoven, A., Hornig, Y., Bermudez, L. E. & Young, L. S. ( 1997; ). Mycobacterium avium reduces expression of costimulatory/adhesion molecules by human monocytes. Cell Immunol 176, 82-91.[CrossRef]
    [Google Scholar]
  28. Mshana, R. N., Hastings, R. C. & Krahenbuhl, J. L. ( 1988; ). Infection with live mycobacteria inhibits in vitro detection of Ia antigen on macrophages. Immunobiology 177, 40-54.[CrossRef]
    [Google Scholar]
  29. Noss, E. H., Harding, C. V. & Boom, W. H. ( 2000; ). Mycobacterium tuberculosis inhibits MHC class II antigen processing in murine bone marrow macrophages. Cell Immunol 201, 63-74.[CrossRef]
    [Google Scholar]
  30. Noss, E. H., Pai, R. K., Sellati, T. J., Radolf, J. D., Belisle, J., Golenbock, D. T., Boom, W. H. & Harding, C. V. ( 2001; ). Toll-like receptor 2-dependent inhibition of macrophage class II MHC expression and antigen processing by 19-kDa lipoprotein of Mycobacterium tuberculosis. J Immunol 167, 910-918.[CrossRef]
    [Google Scholar]
  31. Ochs, H. D., Nonoyama, S., Zhu, Q., Farrington, M. & Wedgwood, R. J. ( 1993; ). Regulation of antibody responses: the role of complement and adhesion molecules. Clin Immunol Immunopathol 67, S33-40.[CrossRef]
    [Google Scholar]
  32. Olakanmi, O., Britigan, B. E. & Schlesinger, L. S. ( 2000; ). Gallium disrupts iron metabolism of mycobacteria residing within human macrophages. Infect Immun 68, 5619-5627.[CrossRef]
    [Google Scholar]
  33. Pancholi, P., Mirza, A., Bhardwaj, N. & Steinman, R. M. ( 1993; ). Sequestration from immune CD4+ T cells of mycobacteria growing in human macrophages. Science 260, 984-986.[CrossRef]
    [Google Scholar]
  34. Pethe, K., Alonso, S., Miet, F., Delogu, G., Brennan, M. J., Locht, C. & Menozzi, F. D. ( 2001; ). The heparin-binding haemagglutinin of M. tuberculosis is required for extrapulmonary dissemination. Nature 412, 190-194.[CrossRef]
    [Google Scholar]
  35. Placido, R., Mancino, G., Amendola, A. & 7 other authors ( 1997; ). Apoptosis of human monocytes/macrophages in Mycobacterium tuberculosis infection. J Pathol 181, 31–38.[CrossRef]
    [Google Scholar]
  36. Plow, E. F., Haas, T. A., Zhang, L., Loftus, J. & Smith, J. W. ( 2000; ). Ligand binding to integrins. J Biol Chem 275, 21785-21788.[CrossRef]
    [Google Scholar]
  37. Pourshafie, M., Ayub, Q. & Barrow, W. W. ( 1993; ). Comparative effects of Mycobacterium avium glycopeptidolipid and lipopeptide fragment on the function and ultrastructure of mononuclear cells. Clin Exp Immunol 93, 72-79.
    [Google Scholar]
  38. Ragno, S., Estrada, I., Butler, R. & Colston, M. J. ( 1997; ). Regulation of macrophage gene expression following invasion by Mycobacterium tuberculosis. Immunol Lett 57, 143-146.[CrossRef]
    [Google Scholar]
  39. Raviglione, M. C., Snider, D. E., Jr & Kochi, A. ( 1995; ). Global epidemiology of tuberculosis: morbidity and mortality of a worldwide epidemic. JAMA (J Am Chem Soc) 273, 220–226.
    [Google Scholar]
  40. Rieu, P., Ueda, T., Haruta, I., Sharma, C. P. & Arnaout, M. A. ( 1994; ). The A-domain of β2 integrin CR3 (CD11b/CD18) is a receptor for the hookworm-derived neutrophil adhesion inhibitor NIF. J Cell Biol 127, 2081-2091.[CrossRef]
    [Google Scholar]
  41. Saha, B., Das, G., Vohra, H., Ganguly, N. K. & Mishra, G. C. ( 1994; ). Macrophage–T cell interaction in experimental mycobacterial infection. Selective regulation of co-stimulatory molecules on Mycobacterium-infected macrophages and its implication in the suppression of cell-mediated immune response. Eur J Immunol 24, 2618-2624.[CrossRef]
    [Google Scholar]
  42. Saunders, B. M. & Cooper, A. M. ( 2000; ). Restraining mycobacteria: role of granulomas in mycobacterial infections. Immunol Cell Biol 78, 334-341.[CrossRef]
    [Google Scholar]
  43. Schauble, T. L., Boom, W. H., Finegan, C. K. & Rich, E. A. ( 1993; ). Characterization of suppressor function of human alveolar macrophages for T lymphocyte responses to phytohemagglutinin: cellular selectivity, reversibility, and early events in T cell activation. Am J Respir Cell Mol Biol 8, 89-97.[CrossRef]
    [Google Scholar]
  44. Schlesinger, L. S. ( 1993; ). Macrophage phagocytosis of virulent but not attenuated strains of Mycobacterium tuberculosis is mediated by mannose receptors in addition to complement receptors. J Immunol 150, 2920-2930.
    [Google Scholar]
  45. Schlesinger, L. S. ( 1996; ). Entry of Mycobacterium tuberculosis into mononuclear phagocytes. Curr Top Microbiol Immunol 215, 71-96.
    [Google Scholar]
  46. Schlesinger, L. S. & Horwitz, M. A. ( 1991; ). Phagocytosis of Mycobacterium leprae by human monocyte-derived macrophages is mediated by complement receptors CR1 (CD35), CR3 (CD11b/CD18), and CR4 (CD11c/CD18) and interferon-gamma activation inhibits complement receptor function and phagocytosis of this bacterium. J Immunol 147, 1983-1994.
    [Google Scholar]
  47. Schlesinger, L. S., Bellinger-Kawahara, C. G., Payne, N. R. & Horwitz, M. A. ( 1990; ). Phagocytosis of Mycobacterium tuberculosis is mediated by human monocyte complement receptors and complement component C3. J Immunol 144, 2771-2780.
    [Google Scholar]
  48. Simon, R. H. & Paine, R.3rd ( 1995; ). Participation of pulmonary alveolar epithelial cells in lung inflammation. J Lab Clin Med 126, 108-118.
    [Google Scholar]
  49. Snider, D. E.Jr & La Montagne, J. R. ( 1994; ). The neglected global tuberculosis problem: a report of the 1992 World Congress on Tuberculosis. J Infect Dis 169, 1189-1196.[CrossRef]
    [Google Scholar]
  50. Speert, D. P. & Silverstein, S. C. ( 1985; ). Phagocytosis of unopsonized zymosan by human monocyte-derived macrophages: maturation and inhibition by mannan. J Leukoc Biol 38, 655-658.
    [Google Scholar]
  51. Stenger, S., Niazi, K. R. & Modlin, R. L. ( 1998; ). Down-regulation of CD1 on antigen-presenting cells by infection with Mycobacterium tuberculosis. J Immunol 161, 3582-3588.
    [Google Scholar]
  52. Stewart, M., Thiel, M. & Hogg, N. ( 1995; ). Leukocyte integrins. Curr Opin Cell Biol 7, 690-696.[CrossRef]
    [Google Scholar]
  53. Stokes, R. W., Haidl, I. D., Jefferies, W. A. & Speert, D. P. ( 1993; ). Mycobacteria–macrophage interactions. Macrophage phenotype determines the nonopsonic binding of Mycobacterium tuberculosis to murine macrophages. J Immunol 151, 7067-7076.
    [Google Scholar]
  54. Teitelbaum, R., Glatman-Freedman, A., Chen, B., Robbins, J. B., Unanue, E., Casadevall, A. & Bloom, B. R. ( 1998; ). A mAb recognizing a surface antigen of Mycobacterium tuberculosis enhances host survival. Proc Natl Acad Sci USA 95, 15688-15693.[CrossRef]
    [Google Scholar]
  55. Thepen, T., Kraal, G. & Holt, P. G. ( 1994; ). The role of alveolar macrophages in regulation of lung inflammation. Ann N Y Acad Sci 725, 200-206.[CrossRef]
    [Google Scholar]
  56. Tsuyuguchi, I., Kawasumi, H., Takashima, T., Tsuyuguchi, T. & Kishimoto, S. ( 1990; ). Mycobacterium aviumMycobacterium intracellulare complex-induced suppression of T-cell proliferation in vitro by regulation of monocyte accessory cell activity. Infect Immun 58, 1369-1378.
    [Google Scholar]
  57. Ueda, T., Rieu, P., Brayer, J. & Arnaout, M. A. ( 1994; ). Identification of the complement iC3b binding site in the β2 integrin CR3 (CD11b/CD18). Proc Natl Acad Sci USA 91, 10680-10684.[CrossRef]
    [Google Scholar]
  58. 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]
  59. Wadee, A. A., Kuschke, R. H. & Dooms, T. G. ( 1995; ). The inhibitory effects of Mycobacterium tuberculosis on MHC class II expression by monocytes activated with riminophenazines and phagocyte stimulants. Clin Exp Immunol 100, 434-439.
    [Google Scholar]
  60. Wang, T., Lafuse, W. P. & Zwilling, B. S. ( 2000; ). Regulation of toll-like receptor 2 expression by macrophages following Mycobacterium avium infection. J Immunol 165, 6308-6313.[CrossRef]
    [Google Scholar]
  61. Wojciechowski, W., DeSanctis, J., Skamene, E. & Radzioch, D. ( 1999; ). Attenuation of MHC class II expression in macrophages infected with Mycobacterium bovis bacillus Calmette–Guerin involves class II transactivator and depends on the Nramp1 gene. J Immunol 163, 2688-2696.
    [Google Scholar]
  62. Zhang, M., Kim, K. J., Iyer, D., Lin, Y., Belisle, J., McEnery, K., Crandall, E. D. & Barnes, P. F. ( 1997; ). Effects of Mycobacterium tuberculosis on the bioelectric properties of the alveolar epithelium. Infect Immun 65, 692-698.
    [Google Scholar]
  63. Zimmerli, S., Edwards, S. & Ernst, J. D. ( 1996; ). Selective receptor blockade during phagocytosis does not alter the survival and growth of Mycobacterium tuberculosis in human macrophages. Am J Respir Cell Mol Biol 15, 760-770.[CrossRef]
    [Google Scholar]
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