Advertisement

Looking Within the Zebrafish to Understand the Tuberculous Granuloma

  • Lalita RamakrishnanEmail author
Chapter
First Online:
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 783)

Abstract

Tuberculosis is characterized by the formation of complex immune cell aggregates called granulomas, which for nearly a century have been viewed as critical host-beneficial structures to restrict bacterial growth and spread. A different view has now emerged from real-time visualization of granuloma formation and its consequences in the optically transparent and genetically tractable zebrafish larva. Pathogenic mycobacteria have developed mechanisms to use host granulomas for their expansion and dissemination, at least during the innate phases of infection. Host processes that are intended to be beneficial—death of infected macrophages and their subsequent phagocytosis by macrophages that are newly recruited to the growing granuloma—are harnessed by mycobacteria for their own benefit. Mycobacteria can also render the granuloma a safe-haven in the more advanced stages of infection. An understanding of the host and bacterial pathways involved in tuberculous granuloma formation may suggest new ways to combat mycobacterial infection.

Keywords

Tubercles Tuburculous granuloma Mycobacterium tuberculosis Macrophages Necrosis Mycobacterium marinum Zebrafish Tumor necrosis factor Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine strain Neutrophils Cell death Host matrix metalloproteinase 9 (MMP9) Apoptosis Mycobacteria 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

The research presented in this chapter has been supported by grants from the National Institutes of Health, including the NIH Director’s Pioneer Award, as well as the Burroughs Wellcome Award in the Pathogenesis of Infectious Diseases, the Ellison Medical Foundation, the Keck Foundation, and the Akibene Foundation. I thank Christine Cosma for discussion and critical review of the manuscript and Tiffany Pecor for help with manuscript preparation.

References

  1. 1.
    Boros DL (ed) (2003) Granulomatous infections and inflammations cellular and molecular mechanisms. ASM Press, Washington, DCGoogle Scholar
  2. 2.
    Adams DO (1976) The granulomatous inflammatory response: a review. Am J Pathol 84:164–192PubMedGoogle Scholar
  3. 3.
    Spector WG (1969) The granulomatous inflammatory exudate. Int Rev Exp Pathol 8:1–55PubMedGoogle Scholar
  4. 4.
    Williams GT, Williams WJ (1983) Granulomatous inflammation—a review. J Clin Pathol 36:723–733PubMedCrossRefGoogle Scholar
  5. 5.
    Adams DO (1974) The structure of mononuclear phagocytes differentiating in vivo I Sequential fine and histologic studies of the effect of Bacillus Calmette-Guerin (BCG). Am J Pathol 76:17–48PubMedGoogle Scholar
  6. 6.
    Cohn ZA (1968) The structure and function of monocytes and macrophages. Adv Immunol 9:163–214PubMedCrossRefGoogle Scholar
  7. 7.
    Dannenberg AM Jr (1968) Cellular hypersensitivity and cellular immunity in the pathogensis of tuberculosis: specificity, systemic and local nature, and associated macrophage enzymes. Bacteriol Rev 32:85–102PubMedGoogle Scholar
  8. 8.
    Bouley DM et al (2001) Dynamic nature of host-pathogen interactions in Mycobacterium marinum granulomas. Infect Immun 69:7820–7831PubMedCrossRefGoogle Scholar
  9. 9.
    Canetti G (1955) The tubercle bacillus in the pulmonary lesion of man; histobacteriology and its bearing on the therapy of pulmonary tuberculosis, American Rev edn. Springer Publishing Company, New York, p 226Google Scholar
  10. 10.
    Hunter RL (2011) Pathology of post primary tuberculosis of the lung: an illustrated critical review. Tuberculosis 91:497–509PubMedCrossRefGoogle Scholar
  11. 11.
    Kumar V, Abbas AK, Fausto N (2005) Robbins and Cotran pathological basis of disease, 7th edn. Elsevier Saunders, PhiladelphiaGoogle Scholar
  12. 12.
    Rich AR (1946) The pathogenesis of tuberculosis, 2nd edn. Charles C Thomas, SpringfieldGoogle Scholar
  13. 13.
    Ramakrishnan L (2012) Revisiting the role of the granuloma in tuberculosis. Nat Rev Immunol 12:352–366PubMedGoogle Scholar
  14. 14.
    Dannenberg AMJ (1993) Immunopathogenesis of pulmonary tuberculosis. Hosp Pract 28:51–58Google Scholar
  15. 15.
    Wolf AJ et al (2007) Mycobacterium tuberculosis infects dendritic cells with high frequency and impairs their function in vivo. J Immunol 179:2509–2519PubMedGoogle Scholar
  16. 16.
    Cosma CL, Sherman DR, Ramakrishnan L (2003) The secret lives of the pathogenic mycobacteria. Annu Rev Microbiol 57:641–676PubMedCrossRefGoogle Scholar
  17. 17.
    Feldman WH, Baggenstoss AH (1938) The reisdual infectivity of the primary complex of tuberculosis. Am J Pathol 14:473–490PubMedGoogle Scholar
  18. 18.
    Opie EL, Aronson JD (1927) Tubercle bacilli in latent tuberculous lesions and in lung tissue without tuberculous lesions. Arch Pathol Lab Med 4:1–21Google Scholar
  19. 19.
    Flynn JL, Chan J (2001) Immunology of tuberculosis. Annu Rev Immunol 19:93–129PubMedCrossRefGoogle Scholar
  20. 20.
    Kaufmann SH (2000) Is the development of a new tuberculosis vaccine possible? Nat Med 6:955–960PubMedCrossRefGoogle Scholar
  21. 21.
    Lawn SD, Butera ST, Shinnick TM (2002) Tuberculosis unleashed: the impact of human immunodeficiency virus infection on the host granulomatous response to Mycobacterium tuberculosis. Microbes Infect 4:635–646PubMedCrossRefGoogle Scholar
  22. 22.
    North RJ, Izzo AA (1993) Granuloma formation in severe combined immunodeficient (SCID) mice in response to progressive BCG infection tendency not to form granulomas in the lung is associated with faster bacterial growth in this organ. Am J Pathol 142:1959–1966PubMedGoogle Scholar
  23. 23.
    Cooper AM et al (1993) Disseminated tuberculosis in interferon gamma gene- disrupted mice. J Exp Med 178:2243–2247PubMedCrossRefGoogle Scholar
  24. 24.
    Cooper AM et al (1997) Interleukin 12 (IL-12) is crucial to the development of protective immunity in mice intravenously infected with Mycobacterium tuberculosis. J Exp Med 186:39–45Google Scholar
  25. 25.
    Flynn JL et al (1993) An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection. J Exp Med 178:2249–2254PubMedCrossRefGoogle Scholar
  26. 26.
    Fremond CM et al (2007) IL-1 receptor-mediated signal is an essential component of MyD88-dependent innate response to Mycobacterium tuberculosis infection. J Immunol 179:1178–1189PubMedGoogle Scholar
  27. 27.
    Fremond CM et al (2004) Fatal Mycobacterium tuberculosis infection despite adaptive immune response in the absence of MyD88. J Clin Invest 114:1790–1799PubMedGoogle Scholar
  28. 28.
    Juffermans N et al (2000) Interleukin-1 signaling is essential for host defense during murine pulmonary tuberculosis. J Infect Dis 182:902–908PubMedCrossRefGoogle Scholar
  29. 29.
    Scanga CA et al (2004) MyD88-deficient mice display a profound loss in resistance to Mycobacterium tuberculosis associated with partially impaired Th1 cytokine and nitric oxide synthase 2 expression. Infect Immun 72:2400–2404PubMedCrossRefGoogle Scholar
  30. 30.
    Sugawara I, Yamada H, Mizuno S (2003) Relative importance of STAT4 in murine tuberculosis. J Med Microbiol 52:29–34Google Scholar
  31. 31.
    Algood HM, Lin L, Flynn JL (2005) Tumor necrosis factor and chemokine interactions in the formation and maintenance of granulomas in tuberculosis. Clin Infect Dis 41:S189–S193PubMedCrossRefGoogle Scholar
  32. 32.
    Bean AG et al (1999) Structural deficiencies in granuloma formation in TNF gene-targeted mice underlie the heightened susceptibility to aerosol Mycobacterium tuberculosis infection, which is not compensated for by lymphotoxin. J Immunol 162:3504–3511PubMedGoogle Scholar
  33. 33.
    Chakravarty SD et al (2008) Tumor necrosis factor blockade in chronic murine tuberculosis enhances granulomatous inflammation and disorganizes granulomas in the lungs. Infect Immun 76:916–926PubMedCrossRefGoogle Scholar
  34. 34.
    Flynn JL et al (1995) Tumor necrosis factor-alpha is required in the protective immune response against Mycobacterium tuberculosis in mice. Immunity 2:561–572PubMedCrossRefGoogle Scholar
  35. 35.
    Kindler V et al (1989) The inducing role of tumor necrosis factor in the development of bactericidal granulomas during BCG infection. Cell 56:731–740PubMedCrossRefGoogle Scholar
  36. 36.
    Roach DR et al (2002) TNF regulates chemokine induction essential for cell recruitment, granuloma formation, and clearance of mycobacterial infection. J Immunol 168:4620–4627PubMedGoogle Scholar
  37. 37.
    Stenger S (2005) Immunological control of tuberculosis: role of tumour necrosis factor and more. Ann Rheum Dis 64:iv24–iv28Google Scholar
  38. 38.
    Clay H, Volkman HE, Ramakrishnan L (2008) Tumor necrosis factor signaling mediates resistance to mycobacteria by inhibiting bacterial growth and macrophage death. Immunity 29:283–294PubMedCrossRefGoogle Scholar
  39. 39.
    Rubin EJ (2009) The granuloma in tuberculosis–friend or foe? N Engl J Med 360:2471–2473PubMedCrossRefGoogle Scholar
  40. 40.
    Bold TD, Ernst JD (2009) Who benefits from granulomas, mycobacteria or host? Cell 136:17–19PubMedCrossRefGoogle Scholar
  41. 41.
    Ulrichs T, Kaufmann SH (2006) New insights into the function of granulomas in human tuberculosis. J Pathol 208:261–269PubMedCrossRefGoogle Scholar
  42. 42.
    Murphy K, Travers P, Walport M (2008) Janeway’s immunobiology, 7th edn. Garland Science Taylor and Francis Group, New YorkGoogle Scholar
  43. 43.
    Mandell GL, Bennett JE, Dolin R (eds) (2010) Mandell, Douglas, and Bennett’s principles and practice of infectious diseases, 7th edn. Churchill Livingston, PhiladelphiaGoogle Scholar
  44. 44.
    Schaff H, Zumla A (eds) (2009) Tuberculosis. Elsevier Saunders, PhiladelphiaGoogle Scholar
  45. 45.
    Longo DL et al (eds) (2012) Harrison’s principles of internal medicine. McGraw-Hill, New YorkGoogle Scholar
  46. 46.
    Tobin DM, Ramakrishnan L (2008) Comparative pathogenesis of Mycobacterium marinum and Mycobacterium tuberculosis. Cell Microbiol 10:1027−1039Google Scholar
  47. 47.
    Ramakrishnan L (1997) Images in clinical medicine Mycobacterium marinum infection of the hand. N Engl J Med 337:612PubMedCrossRefGoogle Scholar
  48. 48.
    Ramakrishnan L et al (1997) Mycobacterium marinum causes both long-term subclinical infection and acute disease in the leopard frog (Rana pipiens). Infect Immun 65:767–773PubMedGoogle Scholar
  49. 49.
    Swaim LE et al (2006) Mycobacterium marinum infection of adult zebrafish causes caseating granulomatous tuberculosis and is moderated by adaptive immunity. Infect Immun 74:6108–6117PubMedCrossRefGoogle Scholar
  50. 50.
    Tobin DM et al (2012) Host genotype-specific therapies can optimize the inflammatory response to mycobacterial infections. Cell 148:434–446PubMedCrossRefGoogle Scholar
  51. 51.
    Tobin DM et al (2010) The lta4 h locus modulates susceptibility to mycobacterial infection in zebrafish and humans. Cell 140:717–730PubMedCrossRefGoogle Scholar
  52. 52.
    Saunders BM et al (2002) CD4 is required for the development of a protective granulomatous response to pulmonary tuberculosis. Cell Immunol 216:65–72PubMedCrossRefGoogle Scholar
  53. 53.
    van Rie A et al (1999) Exogenous reinfection as a cause of recurrent tuberculosis after curative treatment. N Engl J Med 341:1174–1179PubMedCrossRefGoogle Scholar
  54. 54.
    Verver S et al (2005) Rate of reinfection tuberculosis after successful treatment is higher than rate of new tuberculosis. Am J Respir Crit Care Med 171:1430–1435PubMedCrossRefGoogle Scholar
  55. 55.
    Caminero JA et al (2001) Exogenous reinfection with tuberculosis on a European island with a moderate incidence of disease. Am J Respir Crit Care Med 163:717–720PubMedGoogle Scholar
  56. 56.
    Kaufmann SH (2001) How can immunology contribute to the control of tuberculosis? Nat Rev Immunol 1:20–30PubMedCrossRefGoogle Scholar
  57. 57.
    Balasubramanian V et al (1994) Pathogenesis of tuberculosis: pathway to apical localization. Tuber Lung Dis 75:168–178PubMedCrossRefGoogle Scholar
  58. 58.
    Hernandez-Pando R et al (2000) Persistence of DNA from Mycobacterium tuberculosis in superficially normal lung tissue during latent infection. Lancet 356:2133–2138PubMedCrossRefGoogle Scholar
  59. 59.
    McMurray DN (2003) Hematogenous reseeding of the lung in low-dose, aerosol-infected guinea pigs: unique features of the host-pathogen interface in secondary tubercles. Tuberculosis 83:131–134PubMedCrossRefGoogle Scholar
  60. 60.
    Grosset J (2003) Mycobacterium tuberculosis in the extracellular compartment: an underestimated adversary. Antimicrob Agents Chemother 47:833–836PubMedCrossRefGoogle Scholar
  61. 61.
    Cosma CL, Humbert O, Ramakrishnan L (2004) Superinfecting mycobacteria home to established tuberculous granulomas. Nat Immunol 5:828–835PubMedCrossRefGoogle Scholar
  62. 62.
    Cosma CL et al (2008) Trafficking of superinfecting Mycobacterium organisms into established granulomas occurs in mammals and is independent of the Erp and ESX-1 mycobacterial virulence loci. J Infect Dis 198:1851–1855PubMedCrossRefGoogle Scholar
  63. 63.
    Chan K et al (2002) Complex pattern of Mycobacterium marinum gene expression during long-term granulomatous infection. Proc Natl Acad Sci U S A 99:3920–3925PubMedCrossRefGoogle Scholar
  64. 64.
    Ramakrishnan L, Federspiel NA, Falkow S (2000) Granuloma-specific expression of Mycobacterium virulence proteins from the glycine-rich PE- PGRS family. Science 288:1436–1439PubMedCrossRefGoogle Scholar
  65. 65.
    Cooper AM (2009) Cell-mediated immune responses in tuberculosis. Annu Rev Immunol 27:393–422PubMedCrossRefGoogle Scholar
  66. 66.
    Gallegos AM, Pamer EG, Glickman MS (2008) Delayed protection by ESAT-6- specific effector CD4+ T cells after airborne M tuberculosis infection. J Exp Med 205:2359–2368PubMedCrossRefGoogle Scholar
  67. 67.
    Gill W et al (2009) A replication clock for Mycobacterium tuberculosis. Nature Med 15:211–214PubMedCrossRefGoogle Scholar
  68. 68.
    Wolf AJ et al (2008) Initiation of the adaptive immune response to Mycobacterium tuberculosis depends on antigen production in the local lymph node, not the lungs. J Exp Med 205:105–115PubMedCrossRefGoogle Scholar
  69. 69.
    North RJ, Jung YJ (2004) Immunity to tuberculosis. Annu Rev Immunol 22:599–623PubMedCrossRefGoogle Scholar
  70. 70.
    Andersen P (1997) Host responses and antigens involved in protective immunity to Mycobacterium tuberculosis. Scand J Immunol 45:115–131PubMedCrossRefGoogle Scholar
  71. 71.
    Saunders BM, Cooper AM (2000) Restraining mycobacteria: role of granulomas in mycobacterial infections. Immunol Cell Biol 78:334–341PubMedCrossRefGoogle Scholar
  72. 72.
    Davis JM et al (2002) Real-time visualization of mycobacterium-macrophage interactions leading to initiation of granuloma formation in zebrafish embryos. Immunity 17:693–702PubMedCrossRefGoogle Scholar
  73. 73.
    Volkman HE et al (2004) Tuberculous granuloma formation is enhanced by a mycobacterium virulence determinant. PLoS Biol 2:e367PubMedCrossRefGoogle Scholar
  74. 74.
    Davis JM, Ramakrishnan L (2009) The role of the granuloma in expansion and dissemination of early tuberculous infection. Cell 136:37–49PubMedCrossRefGoogle Scholar
  75. 75.
    Egen JG et al (2008) Macrophage and T cell dynamics during the development and disintegration of mycobacterial granulomas. Immunity 28:271–284PubMedCrossRefGoogle Scholar
  76. 76.
    Egen JG et al (2011) Intravital imaging reveals limited antigen presentation and T cell effector function in mycobacterial granulomas. Immunity 34:807–819PubMedCrossRefGoogle Scholar
  77. 77.
    Sherman DR et al (2004) Mycobacterium tuberculosis H37Rv: Delta RD1 is more virulent than M bovis bacille Calmette-Guerin in long-term murine infection. J Infect Dis 190:123–126PubMedCrossRefGoogle Scholar
  78. 78.
    Gao LY et al (2004) A mycobacterial virulence gene cluster extending RD1 is required for cytolysis, bacterial spreading and ESAT-6 secretion. Mol Microbiol 53:1677–1693PubMedCrossRefGoogle Scholar
  79. 79.
    Guinn KM et al (2004) Individual RD1-region genes are required for export of ESAT-6/CFP-10 and for virulence of Mycobacterium tuberculosis. Mol Microbiol 51:359–370PubMedCrossRefGoogle Scholar
  80. 80.
    Choi HH et al (2010) Endoplasmic reticulum stress response is involved in Mycobacterium tuberculosis protein ESAT-6-mediated apoptosis. FEBS Lett 584:2445–2454PubMedCrossRefGoogle Scholar
  81. 81.
    Derrick SC, Morris SL (2007) The ESAT-6 protein of Mycobacterium tuberculosis induces apoptosis of macrophages by activating caspase expression. Cell Microbiol 9:1547–1555PubMedCrossRefGoogle Scholar
  82. 82.
    Mishra BB et al (2010) Mycobacterium tuberculosis protein ESAT-6 is a potent activator of the NLRP3/ASC inflammasome. Cell Microbiol 12:1046–1063PubMedCrossRefGoogle Scholar
  83. 83.
    Behar SM et al (2011) Apoptosis is an innate defense function of macrophages against Mycobacterium tuberculosis. Mucosal Immunol 4:279–287PubMedCrossRefGoogle Scholar
  84. 84.
    Fratazzi C et al (1997) Programmed cell death of Mycobacterium avium serovar 4-infected human macrophages prevents the mycobacteria from spreading and induces mycobacterial growth inhibition by freshly added, uninfected macrophages. J Immunol 158:4320–4327PubMedGoogle Scholar
  85. 85.
    Gan H et al (2008) Mycobacterium tuberculosis blocks crosslinking of annexin-1 and apoptotic envelope formation on infected macrophages to maintain virulence. Nat Immunol 9:1189–1197PubMedCrossRefGoogle Scholar
  86. 86.
    Keane J, Shurtleff B, Kornfeld H (2002) TNF-dependent BALB/c murine macrophage apoptosis following Mycobacterium tuberculosis infection inhibits bacillary growth in an IFN-gamma independent manner. Tuberculosis 82:55–61PubMedCrossRefGoogle Scholar
  87. 87.
    Martin CJ et al (2012) Efferocytosis is an innate antibacterial mechanism. Cell Host and Microbe 12:289−300PubMedCrossRefGoogle Scholar
  88. 88.
    Oddo M et al (1998) Fas ligand-induced apoptosis of infected human macrophages reduces the viability of intracellular Mycobacterium tuberculosis. J Immunol 160:5448–5454PubMedGoogle Scholar
  89. 89.
    Molloy A (1994) Laochumroonvorapong, and G Kaplan, Apoptosis, but not necrosis, of infected monocytes is coupled with killing of intracellular bacillus Calmette-Guerin. J Exp Med 180:1499–1509PubMedCrossRefGoogle Scholar
  90. 90.
    Lammas DA et al (1997) ATP-induced killing of mycobacteria by human macrophages is mediated by purinergic P2Z(P2X7) receptors. Immunity 7:433–444PubMedCrossRefGoogle Scholar
  91. 91.
    Armstrong JA, Hart D (1975) Phagosome-lysosome interactions in cultured macrophages infected with virulent tubercle bacilli Reversal of the usual nonfusion pattern and observations on bacterial survival. J Exp Med 142:1–16PubMedCrossRefGoogle Scholar
  92. 92.
    van der Wel N et al (2007) M tuberculosis and M leprae translocate from the phagolysosome to the cytosol in myeloid cells Cell 129:1287–1298Google Scholar
  93. 93.
    Briken V, Miller JL (2008) Living on the edge: inhibition of host cell apoptosis by Mycobacterium tuberculosis. Futur Microbiol 3:415–422CrossRefGoogle Scholar
  94. 94.
    Hinchey J et al (2007) Enhanced priming of adaptive immunity by a proapoptotic mutant of Mycobacterium tuberculosis. J Clin Invest 117:2279–2288PubMedCrossRefGoogle Scholar
  95. 95.
    Jayakumar D, Jacobs WR Jr, Narayanan S (2008) Protein kinase E of Mycobacterium tuberculosis has a role in the nitric oxide stress response and apoptosis in a human macrophage model of infection. Cell Microbiol 10:365–374PubMedGoogle Scholar
  96. 96.
    Velmurugan K et al (2007) Mycobacterium tuberculosis nuoG is a virulence gene that inhibits apoptosis of infected host cells. PLoS Pathog 3:e110PubMedCrossRefGoogle Scholar
  97. 97.
    Yang CT et al (2012) Neutrophils protect against tuberculosis by oxidative killing of mycobacteria phagocytosed from granuloma macrophages. Cell Host Microbe 12:301−312PubMedCrossRefGoogle Scholar
  98. 98.
    Cree IA et al (1987) Cell death in granulomata: the role of apoptosis. J Clin Pathol 40:1314–1319PubMedCrossRefGoogle Scholar
  99. 99.
    Keane J et al (1997) Infection by Mycobacterium tuberculosis promotes human alveolar macrophage apoptosis. Infect Immun 65:298–304PubMedGoogle Scholar
  100. 100.
    Fayyazi A et al (2000) Apoptosis of macrophages and T cells in tuberculosis associated caseous necrosis. J Pathol 191:417–425PubMedCrossRefGoogle Scholar
  101. 101.
    Clay H et al (2007) Dichotomous role of the macrophage in early Mycobacterium marinum infection of the zebrafish. Cell Host Microbe 2:29–39PubMedCrossRefGoogle Scholar
  102. 102.
    Chen M et al (2008) Lipid mediators in innate immunity against tuberculosis: opposing roles of PGE2 and LXA4 in the induction of macrophage death. J Exp Med 205:2791–2801PubMedCrossRefGoogle Scholar
  103. 103.
    Divangahi M et al (2009) Mycobacterium tuberculosis evades macrophage defenses by inhibiting plasma membrane repair. Nat Immunol 10:899–906PubMedCrossRefGoogle Scholar
  104. 104.
    Divangahi M et al (2010) Eicosanoid pathways regulate adaptive immunity to Mycobacterium tuberculosis. Nat Immunol 11:751–758PubMedCrossRefGoogle Scholar
  105. 105.
    Volkman HE et al (2010) Tuberculous granuloma induction via interaction of a bacterial secreted protein with host epithelium. Science 327:466–469PubMedCrossRefGoogle Scholar
  106. 106.
    Van den Steen E et al (2002) Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9). Crit Rev Biochem Mol Biol 37:375–536PubMedCrossRefGoogle Scholar
  107. 107.
    Banaiee N et al (2006) Potent inhibition of macrophage responses to IFN-gamma by live virulent Mycobacterium tuberculosis is independent of mature mycobacterial lipoproteins but dependent on TLR2. J Immunol 176:3019–3027PubMedGoogle Scholar
  108. 108.
    Fortune SM et al (2004) Mycobacterium tuberculosis inhibits macrophage responses to IFN-gamma through myeloid differentiation factor 88-dependent and -independent mechanisms. J Immunol 172:6272–6280PubMedGoogle Scholar
  109. 109.
    Kincaid EZ, Ernst JD (2003) Mycobacterium tuberculosis exerts gene-selective inhibition of transcriptional responses to IFN-gamma without inhibiting STAT1 function. J Immunol 171:2042–2049PubMedGoogle Scholar
  110. 110.
    Ting LM et al (1999) Mycobacterium tuberculosis inhibits IFN-gamma transcriptional responses without inhibiting activation of STAT1. J Immunol 163:3898–3906PubMedGoogle Scholar
  111. 111.
    Stockhammer OW et al (2009) Transcriptome profiling and functional analyses of the zebrafish embryonic innate immune response to Salmonella infection. J Immunol 182:5641–5653PubMedCrossRefGoogle Scholar
  112. 112.
    Taylor JL et al (2006) Role for matrix metalloproteinase 9 in granuloma formation during pulmonary Mycobacterium tuberculosis infection. Infect Immun 74:6135–6144PubMedCrossRefGoogle Scholar
  113. 113.
    Park KJ et al (2005) Expression of matrix metalloproteinase-9 in pleural effusions of tuberculosis and lung cancer. Respiration 72:166–175PubMedCrossRefGoogle Scholar
  114. 114.
    Price NM et al (2001) Identification of a matrix-degrading phenotype in human tuberculosis in vitro and in vivo. J Immunol 166:4223–4230PubMedGoogle Scholar
  115. 115.
    Sheen P et al (2009) High MMP-9 activity characterises pleural tuberculosis correlating with granuloma formation. Eur Respir J 33:134–141PubMedCrossRefGoogle Scholar
  116. 116.
    Elkington T et al (2007) Synergistic up-regulation of epithelial cell matrix metalloproteinase-9 secretion in tuberculosis. Am J Respir Cell Mol BiolGoogle Scholar
  117. 117.
    Adams KN et al (2011) Drug tolerance in replicating mycobacteria mediated by a macrophage-induced efflux mechanism. Cell 145:39–53PubMedCrossRefGoogle Scholar
  118. 118.
    Chackerian AA et al (2002) Dissemination of Mycobacterium tuberculosis is influenced by host factors and precedes the initiation of T-cell immunity. Infect Immun 70:4501–4509PubMedCrossRefGoogle Scholar
  119. 119.
    Schreiber HA et al (2011) Inflammatory dendritic cells migrate in and out of transplanted chronic mycobacterial granulomas in mice. J Clin Invest 121:3902–3913PubMedCrossRefGoogle Scholar
  120. 120.
    Akira M, Sakatani M, Ishikawa H (2000) Transient radiographic progression during initial treatment of pulmonary tuberculosis: CT findings. J Comput Assist Tomogr 24:426–431PubMedCrossRefGoogle Scholar
  121. 121.
    Bobrowitz ID (1980) Reversible roentgenographic progression in the initial treatment of pulmonary tuberculosis. Am Rev Respir Dis 121:735–742PubMedGoogle Scholar
  122. 122.
    Russell DG (2007) Who puts the tubercle in tuberculosis? Nat Rev Microbiol 5:39–47PubMedCrossRefGoogle Scholar
  123. 123.
    Takaki K et al (2012) An in vivo platform for rapid high-throughput antitubercular drug discovery. Cell Rep 2:175–184PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Microbiology, Medicine and ImmunologyUniversity of WashingtonSeattleUSA

Personalised recommendations

Cite chapter

Buy options