Chapter 27 : Intracellular Models of Infection

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in

Intracellular Models of Infection, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555817657/9781555812959_Chap27-1.gif /docserver/preview/fulltext/10.1128/9781555817657/9781555812959_Chap27-2.gif


Intracellular models of infection have proven to be invaluable tools to address diverse questions in mycobacterial research. This chapter begins with an analysis of basic host-pathogen interactions in the infected murine macrophage. It then describes two models in which infected human monocytes interact with lymphocytes and other cells to generate antimycobacterial activity. Lastly, the chapter summarizes clinical trials in which these models were used to analyze the effects of BCG vaccination and other immunologic interventions. The best-studied macrophage antimycobacterial mechanisms are those mediated by (i) the production of nitric oxide (NO) and related reactive nitrogen intermediates (RNI) and (ii) phagolysosomal fusion. Recent microarray analyses have demonstrated that RNI can regulate gene expression in vitro. It is becoming clear that can interfere with the tethering and fusion machinery involved in phagolysosomal biogenesis. Natural killer (NK) cells have the capacity to kill intracellular , whether these cells are isolated from PPD-positive or PPD-negative subjects. The ability of tuberculin reactors to control growth could be blocked by antibodies to gamma interferon (IFN-γ) or tumor necrosis factor (TNF-α) and could be inhibited by methylprednisolone or pentoxifylline. Impaired control of infection was not reconstituted by the addition of exogenous IFN-γ but, in a small cohort, improved following initiation of antiretroviral therapy.

Citation: Chan J, Silver R, Kampmann B, Wallis R. 2005. Intracellular Models of Infection, p 437-450. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch27

Key Concept Ranking

Nitric Oxide Synthase
Cytotoxic T Cell
Tumor Necrosis Factor
Methionine Sulfoxide Reductase
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1
Figure 1

After phagocytosis, the tubercle bacillus is subject to attack by reactive radicals including various reactive nitrogen intermediates (RNI) and the hydrolytic enzymes of the lysosome. has evolved sophisticated means by which these potent antimicrobial activities of macrophages can be evaded.

Citation: Chan J, Silver R, Kampmann B, Wallis R. 2005. Intracellular Models of Infection, p 437-450. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch27
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Altare, F.,, A. Durandy,, D. Lammas,, J. F. Emile,, S. Lamhamedi,, F. Le Deist,, P. Drysdale,, E. Jouanguy,, R. Doffinger,, F. Bernaudin,, O. Jeppsson,, J. A. Gollob,, E. Meinl,, A. W. Segal,, A. Fischer,, D. Kumararatne,, and J. L. Casanova. 1998. Impairment of mycobacterial immunity in human interleukin-12 receptor deficiency. Science 280:14321435.
2. Armstrong, J. A.,, and P. D. Hart. 1971. Response of cultured macrophages to Mycobacterium tuberculosis, with observations on fusion of lysosomes with phagosomes. J. Exp. Med. 134:713740.
3. Bainton, D. F. 1981. The discovery of lysosomes. J. Cell Biol. 91:66s76s.
4. Barker, K.,, H. Fan,, C. Carroll,, G. Kaplan,, J. Barker,, W. Hellmann,, and Z. A. Cohn. 1996. Nonadherent cultures of human monocytes kill Mycobacterium smegmatis, but adherent cultures do not. Infect. Immun. 64:428433.
5. Beckman, J. S.,, and W. H. Koppenol. 1996. Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am. J. Physiol. 271:C1424C1437.
6. Bellamy, R.,, C. Ruwende,, T. Corrah,, K. P. McAdam,, H. C. Whittle,, and A. V. Hill. 1998. Variations in the NRAMP1 gene and susceptibility to tuberculosis in West Africans. N. Engl. J. Med. 338:640644.
7. Bonecini-Almeida, M. G.,, S. Chitale,, I. Boutsikakis,, J. Geng,, H. Doo,, S. He,, and J. L. Ho. 1998. Induction of in vitro human macrophage anti-Mycobacterium tuberculosis activity: requirement for IFN-gamma and primed lymphocytes. J. Immunol. 160:44904499.
8. Brill, K. J.,, Q. Li,, R. Larkin,, D. H. Canaday,, D. R. Kaplan,, W. H. Boom,, and R. F. Silver. 2001. Human natural killer cells mediate killing of intracellular Mycobacterium tuberculosis H37Rv via granule-independent mechanisms. Infect. Immun. 69:17551765.
9. Bryk, R.,, P. Griffin,, and C. Nathan. 2000. Peroxynitrite reductase activity of bacterial peroxiredoxins. Nature 407: 211215.
10. Bryk, R.,, C. D. Lima,, H. Erdjument-Bromage,, P. Tempst,, and C. Nathan. 2002. Metabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein. Science 295:10731077.
11. Canaday, D. H.,, R. Beigi,, R. F. Silver,, C. V. Harding,, W. H. Boom,, and G. R. Dubyak. 2002. ATP and control of intracellular growth of mycobacteria by T cells. Infect. Immun. 70:64566459.
12. Canaday, D. H.,, R. J. Wilkinson,, Q. Li,, C. V. Harding,, R. F. Silver,, and W. H. Boom. 2001. CD4+ and CD8+ T cells kill intracellular Mycobacterium tuberculosis by a perforin and Fas/Fas ligand-independent mechanism. J. Immunol. 167: 27342742.
13. Chan, J.,, and J. Flynn,. 1999. Nitric oxide in Mycobacterium tuberculosis infection, p. 281310. In F. Fang (ed.), Nitric Oxide and Infection. Plenum Publishing Corp., New York, N.Y.
14. Chan, J.,, K. Tanaka,, D. Carroll,, J. Flynn,, and B. R. Bloom. 1995. Effects of nitric oxide synthase inhibitors on murine infection with Mycobacterium tuberculosis. Infect. Immun. 63:736740.
15. Chan, J.,, Y. Xing,, R. S. Magliozzo,, and B. R. Bloom. 1992. Killing of virulent Mycobacterium tuberculosis by reactive nitrogen intermediates produced by activated murine macrophages. J. Exp. Med. 175:11111122.
16. Chen, L.,, Q. W. Xie,, and C. Nathan. 1998. Alkyl hydroperoxide reductase subunit C (AhpC) protects bacterial and human cells against reactive nitrogen intermediates. Mol. Cell 1:795805.
17. Cheon, S. H.,, B. Kampmann,, A. G. Hise,, M. Phillips,, H. Y. Song,, K. Landen,, Q. Li,, R. Larkin,, J. J. Ellner,, R. F. Silver,, D. F. Hoft,, and R. S. Wallis. 2002. Bactericidal activity in whole blood as a potential surrogate marker of immunity after vaccination against tuberculosis. Clin. Diagn. Lab. Immunol. 9:901907.
18. Choi, H. S.,, P. R. Rai,, H. W. Chu,, C. Cool,, and E. D. Chan. 2002. Analysis of nitric oxide synthase and nitrotyrosine expression in human pulmonary tuberculosis. Am. J. Respir. Crit. Care Med. 166:178186.
19. Christoforidis, S.,, H. M. McBride,, R. D. Burgoyne,, and M. Zerial. 1999. The Rab5 effector EEA1 is a core component of endosome docking. Nature 397:621625.
20. Clemens, D. L.,, B. Y. Lee,, and M. A. Horwitz. 2000. Deviant expression of Rab5 on phagosomes containing the intracellular pathogens Mycobacterium tuberculosis and Legionella pneumophila is associated with altered phagosomal fate. Infect. Immun. 68:26712684.
21. Clemens, D. L.,, B. Y. Lee,, and M. A. Horwitz. 2000. Mycobacterium tuberculosis and Legionella pneumophila phagosomes exhibit arrested maturation despite acquisition of Rab7. Infect. Immun. 68:51545166.
22. Cole, S. T.,, R. Brosch,, J. Parkhill,, T. Garnier,, C. Churcher,, D. Harris,, S. V. Gordon,, K. Eiglmeier,, S. Gas,, C. E. Barry,, F. Tekaia,, K. Badcock,, D. Basham,, D. Brown,, T. Chillingworth,, R. Connor,, R. Davies,, K. Devlin,, T. Feltwell,, S. Gentles,, N. Hamlin,, S. Holroyd,, T. Hornsby,, K. Jagels,, A. Krogh,, J. McLean,, S. Moule,, L. Murphy,, K. Oliver,, J. Osborne,, M. A. Quail,, M.-A. Rajandream,, J. Rogers,, S. Rutter,, K. Seeger,, J. Skelton,, R. Squares,, S. Squares J. E. Sulston, K. Taylor, S. Whitehead, and B. G. Barrell. 1998. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393:537544.
23. Crowle, A. 1981. Preliminary demonstration of human tuberculoimmunity in vitro. Infect. Immun. 31:453464.
24. Crowle, A.,, E. R. Ross,, and M. H. May. 1987. Inhibition by 1,25-(OH)2 vitamin D3 of the multiplication of virulent tubercle bacilli in cultured human macrophages. Infect. Immun. 55:29452950.
25. De Duve, C.,, and R. Wattiaux. 1966. Functions of lysosomes. Annu. Rev. Physiol. 28:435492.
26. de Hostos, E. L. 1999. The coronin family of actin-associated proteins. Trends Cell Biol. 9:345350.
27. de Jong, R.,, F. Altare,, I. A. Haagen,, D. G. Elferink,, T. Boer,, V. van Breda,, P. J. Kabel,, J. M. Draaisma,, J. T. van Dissel,, F. P. Kroon,, J. L. Casanova,, and T. H. Ottenhoff. 1998. Severe mycobacterial and Salmonella infections in interleukin- 12 receptor-deficient patients. Science 280:14351438.
28. Denis, M. 1991. Killing of Mycobacterium tuberculosis within human monocytes: activation by cytokines and calcitriol. Clin. Exp. Immunol. 84:200206.
29. Deretic, V.,, and R. A. Fratti. 1999. Mycobacterium tuberculosis phagosome. Mol. Microbiol. 31:16031609.
30. Desjardins, M. 1995. Biogenesis of phagolysosomes: the “kiss and run” hypothesis. Trends Cell Biol. 5:183186.
31. Desjardins, M.,, L. A. Huber,, R. G. Parton,, and G. Griffiths. 1994. Biogenesis of phagolysosomes proceeds through a sequential series of interactions with the endocytic apparatus. J. Cell Biol. 124:677688.
32. Dieli, F.,, M. Troye-Blomberg,, S. E. Farouk,, G. Sirecil,, and A. Salerno. 2001. Biology of gammadelta T cells in tuberculosis and malaria. Curr. Mol. Med. 1:437446.
33. Dorman, S. E.,, and S. M. Holland. 1998. Mutation in the signal-transducing chain of the interferon-gamma receptor and susceptibility to mycobacterial infection. J. Clin. Investig. 101:23642369.
34. Douvas, G. S.,, D. L. Looker,, A. E. Vatter,, and A. J. Crowle. 1985. Gamma interferon activates human macrophages to become tumoricidal and leishmanicidal but enhances replication of macrophage-associated mycobacteria. Infect. Immun. 50:18.
35. Ehrt, S.,, M. U. Shiloh,, J. Ruan,, M. Choi,, S. Gunzburg,, C. Nathan,, Q. Xie,, and L. W. Riley. 1997. A novel antioxidant gene from Mycobacterium tuberculosis. J. Exp. Med. 186:18851896.
36. Ellner, J. J.,, C. S. Hirsch,, and C. C. Whalen. 2000. Correlates of protective immunity to Mycobacterium tuberculosis in humans. Clin. Infect. Dis. 30(Suppl. 3):S279S282.
37. Ferrari, G.,, H. Langen,, M. Naito,, and J. Pieters. 1999. A coat protein on phagosomes involved in the intracellular survival of mycobacteria. Cell 97:435447.
38. Flynn, J. L.,, and J. Chan. 2001. Immunology of tuberculosis. Annu. Rev. Immunol. 19:93129.
39. Flynn, J. L.,, C. A. Scanga,, K. E. Tanaka,, and J. Chan. 1998. Effects of aminoguanidine on latent murine tuberculosis. J. Immunol. 160:17961803.
40. Fratti, R. A.,, J. M. Backer,, J. Gruenberg,, S. Corvera,, and V. Deretic. 2001. Role of phosphatidylinositol 3-kinase and Rab5 effectors in phagosomal biogenesis and mycobacterial phagosome maturation arrest. J. Cell Biol. 154: 631644.
41. Fratti, R. A.,, J. Chua,, and V. Deretic. 2002. Cellubrevin alterations and Mycobacterium tuberculosis phagosome maturation arrest. J. Biol. Chem. 277:1732017326.
42. Fratti, R. A.,, J. Chua,, and V. Deretic. 2003. Induction of p38 mitogen-activated protein kinase reduces early endosome autoantigen 1 (EEA1) recruitment to phagosomal membranes. J. Biol. Chem. 278:4696146967.
43. Fratti, R. A.,, J. Chua,, I. Vergne,, and V. Deretic. 2003. Mycobacterium tuberculosis glycosylated phosphatidylinositol causes phagosome maturation arrest. Proc. Natl. Acad. Sci. USA 100:54375442.
44. Fratti, R. A.,, I. Vergne,, J. Chua,, J. Skidmore,, and V. Deretic. 2000. Regulators of membrane trafficking and Mycobacterium tuberculosis phagosome maturation block. Electrophoresis 21:33783385.
45. Frehel, C.,, C. De Chastellier,, T. Lang,, and N. Rastogi. 1986. Evidence for inhibition of fusion of lysosomal and prelysosomal compartments with phagosomes in macrophages infected with pathogenic Mycobacterium avium. Infect. Immun. 52:252262.
46. Hart, P. D.,, J. A. Armstrong,, C. A. Brown,, and P. Draper. 1972. Ultrastructural study of the behavior of macrophages toward parasitic mycobacteria. Infect. Immun. 5:803807.
47. Hirsch, C. S.,, J. J. Ellner,, D. G. Russell,, and E. A. Rich. 1994. Complement receptor-mediated uptake and tumor necrosis factor-alpha-mediated growth inhibition of Mycobacterium tuberculosis by human alveolar macrophages. J. Immunol. 152:743753.
48. Hoft, D. F.,, S. Worku,, B. Kampmann,, C. C. Whalen,, J. J. Ellner,, C. S. Hirsch,, R. B. Brown,, R. Larkin,, Q. Li,, H. Yun,, and R. F. Silver. 2002. Investigation of the relationships between immune-mediated inhibition of mycobacterial growth and other potential surrogate markers of protective Mycobacterium tuberculosis immunity. J. Infect. Dis. 186:14481457.
49. Jacobson, F. S.,, R. W. Morgan,, M. F. Christman,, and B. N. Ames. 1989. An alkyl hydroperoxide reductase from Salmonella typhimurium involved in the defense of DNA against oxidative damage. Purification and properties. J. Biol. Chem. 264:14881496.
50. Jahn, R.,, and T. C. Sudhof. 1999. Membrane fusion and exocytosis. Annu. Rev. Biochem. 68:863911.
51. Jouanguy, E.,, S. Lamhamedi-Cherradi,, D. Lammas,, S. E. Dorman,, M. C. Fondaneche,, S. Dupuis,, R. Doffinger,, F. Altare,, J. Girdlestone,, J. F. Emile,, H. Ducoulombier,, D. Edgar,, J. Clarke,, V. A. Oxelius,, M. Brai,, V. Novelli,, K. Heyne,, A. Fischer,, S. M. Holland,, D. S. Kumararatne,, R. D. Schreiber,, and J. L. Casanova. 1999. A human IFNGR1 small deletion hotspot associated with dominant susceptibility to mycobacterial infection. Nat. Genet. 21: 370378.
52. Kampmann, B.,, P. O. Gaora,, V. A. Snewin,, M. P. Gares,, D. B. Young,, and M. Levin. 2000. Evaluation of human antimycobacterial immunity using recombinant reporter mycobacteria. J. Infect. Dis. 182:895901.
52.a. Kampmann, B.,, G. Tena,, S. Mzazi,, D. Young,, B. Eley,, and M. Levin. Novel human in vitro system to evaluate antimycobacterial vaccines. Infect. Immun., in press.
53. Kornfeld, S. 1987. Trafficking of lysosomal enzymes. FASEB J. 1:462468.
54. Kusner, D. J.,, and J. Adams. 2000. ATP-induced killing of virulent Mycobacterium tuberculosis within human macrophages requires phospholipase D. J. Immunol. 164:379388.
55. Kusner, D. J.,, and J. A. Barton. 2001. ATP stimulates human macrophages to kill intracellular virulent Mycobacterium tuberculosis via calcium-dependent phagosome-lysosome fusion. J. Immunol. 167:33083315.
56. Lammas, D.,, C. Stober,, C. J. Harvey,, N. Kendrick,, S. Panchalingam,, and D. S. Kumararatne. 1997. ATP-induced killing of mycobacteria by human macrophages is mediated by purinergic P2Z (P2X7) receptors. Immunity 7:433444.
57. Larkin, R.,, C. D. Benjamin,, Y. M. Hsu,, Q. Li,, L. Zukowski,, and R. F. Silver. 2002. CD40 ligand (CD154) does not contribute to lymphocyte-mediated inhibition of virulent Mycobacterium tuberculosis within human monocytes. Infect. Immun. 70:47164720.
58. Lawe, D. C.,, V. Patki,, R. Heller-Harrison,, D. Lambright,, and S. Corvera. 2000. The FYVE domain of early endosome antigen 1 is required for both phosphatidylinositol 3-phosphate and Rab5 binding. Critical role of this dual interaction for endosomal localization. J. Biol. Chem. 275:36993705.
59. MacMicking, J.,, Q. W. Xie,, and C. Nathan. 1997. Nitric oxide and macrophage function. Annu. Rev. Immunol. 15: 323350.
60. MacMicking, J. D.,, R. J. North,, R. LaCourse,, J. S. Mudgett,, S. K. Shah,, and C. F. Nathan. 1997. Identification of nitric oxide synthase as a protective locus against tuberculosis. Proc. Natl. Acad. Sci. USA 94:52435248.
61. MacMicking, J. D.,, G. A. Taylor,, and J. D. McKinney. 2003. Immune control of tuberculosis by IFN-gamma-inducible LRG-47. Science 302:654659.
62. Malik, Z. A.,, G. M. Denning,, and D. J. Kusner. 2000. Inhibition of Ca2+ signaling by Mycobacterium tuberculosis is associated with reduced phagosome-lysosome fusion and increased survival within human macrophages. J. Exp. Med. 191:287302.
63. Malik, Z. A.,, S. S. Iyer,, and D. J. Kusner. 2001. Mycobacterium tuberculosis phagosomes exhibit altered calmodulindependent signal transduction: contribution to inhibition of phagosome-lysosome fusion and intracellular survival in human macrophages. J. Immunol. 166:33923401.
64. Malik, Z. A.,, C. R. Thompson,, S. Hashimi,, B. Porter,, S. S. Iyer,, and D. J. Kusner. 2003. Cutting edge: Mycobacterium tuberculosis blocks Ca2+ signaling and phagosome maturation in human macrophages via specific inhibition of sphingosine kinase. J. Immunol. 170:28112815.
65. McBride, H. M.,, V. Rybin,, C. Murphy,, A. Giner,, R. Teasdale,, and M. Zerial. 1999. Oligomeric complexes link Rab5 effectors with NSF and drive membrane fusion via interactions between EEA1 and syntaxin 13. Cell 98:377386.
66. Mellman, I.,, R. Fuchs,, and A. Helenius. 1986. Acidification of the endocytic and exocytic pathways. Annu. Rev. Biochem. 55:663700.
67. Molloy, A.,, P. Laochumroonvorapong,, and G. Kaplan. 1994. Apoptosis, but not necrosis, of infected monocytes is coupled with killing of intracellular bacillus Calmette- Guérin. J. Exp. Med. 180:14991509.
68. Newport, M. J.,, C. M. Huxley,, S. Huston,, C. M. Hawrylowicz,, B. A. Oostra,, R. Williamson,, and M. Levin. 1996. A mutation in the interferon-gamma-receptor gene and susceptibility to mycobacterial infection. N. Engl. J. Med. 335:19411949.
69. Nicholson, S.,, M. G. Bonecini-Almeida,, J. R. Lapa e Silva,, C. Nathan,, Q. W. Xie,, R. Mumford,, J. R. Weidner,, J. Calaycay,, J. Geng,, N. Boechat,, C. Linhares,, W. Rom,, and J. L. Ho. 1996. Inducible nitric oxide synthase in pulmonary alveolar macrophages from patients with tuberculosis. J. Exp. Med. 183:22932302.
70. Nielsen, E.,, S. Christoforidis,, S. Uttenweiler-Joseph,, M. Miaczynska,, F. Dewitte,, M. Wilm,, B. Hoflack,, and M. Zerial. 2000. Rabenosyn-5, a novel Rab5 effector, is complexed with hVPS45 and recruited to endosomes through a FYVE finger domain. J. Cell. Biol. 151:601612.
71. Nozaki, Y.,, Y. Hasegawa,, S. Ichiyama,, I. Nakashima,, and K. Shimokata. 1997. Mechanism of nitric oxide-dependent killing of Mycobacterium bovis BCG in human alveolar macrophages. Infect. Immun. 65:36443647.
72. O’Brien, L.,, J. Carmichael,, D. B. Lowrie,, and P. W. Andrew. 1994. Strains of Mycobacterium tuberculosis differ in susceptibility to reactive nitrogen intermediates in vitro. Infect. Immun. 62:51875190.
73. Ohkuma, S.,, and B. Poole. 1978. Fluorescence probe measurement of the intralysosomal pH in living cells and the perturbation of pH by various agents. Proc. Natl. Acad. Sci. USA 75:33273331.
74. Ohno, H.,, G. Zhu,, V. P. Mohan,, D. Chu,, S. Kohno,, W. R. Jacobs, Jr.,, and J. Chan. 2003. The effects of reactive nitrogen intermediates on gene expression in Mycobacterium tuberculosis. Cell Microbiol. 5:637648.
75. Ouellet, H.,, Y. Ouellet,, C. Richard,, M. Labarre,, B. Wittenberg,, J. Wittenberg,, and M. Guertin. 2002. Truncated hemoglobin HbN protects Mycobacterium bovis from nitric oxide. Proc. Natl. Acad. Sci. USA 99:59025907.
76. Rich, E. A.,, M. Torres,, E. Sada,, C. K. Finegan,, B. D. Hamilton,, and Z. Toossi. 1997. Mycobacterium tuberculosis (MTB)-stimulated production of nitric oxide by human alveolar macrophages and relationship of nitric oxide production to growth inhibition of MTB. Tubercle Lung Dis. 78:247255.
77. Rockett, K. A.,, R. Brookes,, I. Udalova,, V. Vidal,, A. V. Hill,, and D. Kwiatkowski. 1998. 1,25-Dihydroxyvitamin D3 induces nitric oxide synthase and suppresses growth of Mycobacterium tuberculosis in a human macrophage-like cell line. Infect. Immun. 66:53145321.
78. Rook, G.,, J. Steele,, M. Ainsworth,, and B. R. Champion. 1986. Activation of macrophages to inhibit proliferation of Mycobacterium tuberculosis: comparison of the effects of recombinant interferon gamma on human monocytes and murine peritoneal macrophages. Immunology 59:333338.
79. Ruan, J.,, G. St John,, S. Ehrt,, L. Riley,, and C. Nathan. 1999. noxR3, a novel gene from Mycobacterium tuberculosis, protects Salmonella typhimurium from nitrosative and oxidative stress. Infect. Immun. 67:32763283.
80. Russell, D. G. 2001. Mycobacterium tuberculosis: here today, and here tomorrow. Nat. Rev. Mol. Cell Biol. 2:569577.
81. Russell, D. G.,, H. C. Mwandumba,, and E. E. Rhoades. 2002. Mycobacterium and the coat of many lipids. J. Cell Biol. 158:421426.
82. Scanga, C. A.,, V. P. Mohan,, K. Tanaka,, D. Alland,, J. L. Flynn,, and J. Chan. 2001. The inducible nitric oxide synthase locus confers protection against aerogenic challenge of both clinical and laboratory strains of Mycobacterium tuberculosis in mice. Infect. Immun. 69:77117717.
83. Schaible, U. E.,, S. Sturgill-Koszycki,, P. H. Schlesinger,, and D. G. Russell. 1998. Cytokine activation leads to acidification and increases maturation of Mycobacterium aviumcontaining phagosomes in murine macrophages. J. Immunol. 160:12901296.
84. Schuller, S.,, J. Neefjes,, T. Ottenhoff,, J. Thole,, and D. Young. 2001. Coronin is involved in uptake of Mycobacterium bovis BCG in human macrophages but not in phagosome maintenance. Cell Microbiol. 3:785793.
85. Silver, R. F.,, Q. Li,, W. H. Boom,, and J. J. Ellner. 1998. Lymphocyte-dependent inhibition of growth of virulent Mycobacterium tuberculosis H37Rv within human monocytes: requirement for CD4+ T cells in purified protein derivative-positive, but not in purified protein derivative-negative, subjects. J. Immunol. 160:24082417.
86. Simonsen, A.,, J. M. Gaullier,, A. D’Arrigo,, and H. Stenmark. 1999. The Rab5 effector EEA1 interacts directly with syntaxin- 6. J. Biol. Chem. 274:2885728860.
87. Simonsen, A.,, R. Lippe,, S. Christoforidis,, J. M. Gaullier,, A. Brech,, J. Callaghan,, B. H. Toh,, C. Murphy,, M. Zerial,, and H. Stenmark. 1998. EEA1 links PI(3)K function to Rab5 regulation of endosome fusion. Nature 394:494498.
88. Stead, W. W. 1981. Tuberculosis among elderly persons: an outbreak in a nursing home. Ann. Intern. Med. 94:606610.
89. Stenger, S.,, R. J. Mazzaccaro,, K. Uyemura,, S. Cho,, P. F. Barnes,, J. P. Rosat,, A. Sette,, M. B. Brenner,, S. A. Porcelli,, B. R. Bloom,, and R. L. Modlin. 1997. Differential effects of cytolytic T cell subsets on intracellular infection. Science 276:16841687.
90.St. John, G., N. Brot, J. Ruan, H. Erdjument-Bromage, P. Tempst, H. Weissbach, and C. Nathan. 2001. Peptide methionine sulfoxide reductase from Escherichia coli and Mycobacterium tuberculosis protects bacteria against oxidative damage from reactive nitrogen intermediates. Proc. Natl. Acad. Sci. USA 98:99019906.
91. Storz, G.,, M. F. Christman,, H. Sies,, and B. N. Ames. 1987. Spontaneous mutagenesis and oxidative damage to DNA in Salmonella typhimurium. Proc. Natl. Acad. Sci. USA 84: 89178921.
92. Sturgill-Koszycki, S.,, P. H. Schlesinger,, P. Chakraborty,, P. L. Haddix,, H. L. Collins,, A. K. Fok,, R. D. Allen,, S. L. Gluck,, J. Heuser,, and D. G. Russell. 1994. Lack of acidification in Mycobacterium phagosomes produced by exclusion of the vesicular proton-ATPase. Science 263:678681.
93. Tartaglia, L. A.,, G. Storz,, M. H. Brodsky,, A. Lai,, and B. N. Ames. 1990. Alkyl hydroperoxide reductase from Salmonella typhimurium. Sequence and homology to thioredoxin reductase and other flavoprotein disulfide oxidoreductases. J. Biol. Chem. 265:1053510540.
94. Tena, G. N.,, D. B. Young,, B. Eley,, H. F. Henderson,, M. Nicol,, M. Levin,, and B. Kampmann. 2003. Failure to control growth of mycobacteria in blood from children infected with HIV, and its relationship to T cell function. J. Infect. Dis. 187:15441551.
95. Vergne, I.,, R. A. Fratti,, P. J. Hill,, J. Chua,, J. Belisle,, and V. Deretic. 2004. Mycobacterium tuberculosis phagosome maturation arrest: mycobacterial phosphatidylinositol analog phosphatidylinositol mannoside stimulates early endosomal fusion. Mol. Biol. Cell 15:751760.
96. Via, L. E.,, D. Deretic,, R. J. Ulmer,, N. S. Hibler,, L. A. Huber,, and V. Deretic. 1997. Arrest of mycobacterial phagosome maturation is caused by a block in vesicle fusion between stages controlled by rab5 and rab7. J. Biol. Chem. 272: 1332613331.
97. Vieira, O. V.,, R. J. Botelho,, and S. Grinstein. 2002. Phagosome maturation: aging gracefully. Biochem. J. 366:689704.
98. Voskuil, M. I.,, D. Schnappinger,, K. C. Visconti,, M. I. Harrell,, G. M. Dolganov,, D. R. Sherman,, and G. K. Schoolnik. 2003. Inhibition of respiration by nitric oxide induces a Mycobacterium tuberculosis dormancy program. J. Exp. Med. 198:705713.
99. Wallis, R. S.,, M. Palaci,, S. Vinhas,, A. G. Hise,, F. C. Ribeiro,, K. Landen,, S. H. Cheon,, H. Y. Song,, M. Phillips,, R. Dietze,, and J. J. Ellner. 2001. A whole blood bactericidal assay for tuberculosis. J. Infect Dis. 183:13001303.
100. Wang, C. H.,, C. Y. Liu,, H. C. Lin,, C. T. Yu,, K. F. Chung,, and H. P. Kuo. 1998. Increased exhaled nitric oxide in active pulmonary tuberculosis due to inducible NO synthase upregulation in alveolar macrophages. Eur. Respir. J. 11:809815.
101. Warwick-Davies, J.,, J. Dhillon,, L. O’Brien,, P. W. Andrew,, and D. B. Lowrie. 1994. Apparent killing of Mycobacterium tuberculosis by cytokine-activated human monocytes can be an artefact of a cytotoxic effect on the monocytes. Clin. Exp. Immunol. 96:214217.
102. Xu, S.,, A. Cooper,, S. Sturgill Koszycki,, T. van Heyningen,, D. Chatterjee,, I. Orme,, P. Allen,, and D. G. Russell. 1994. Intracellular trafficking in Mycobacterium tuberculosis and Mycobacterium avium-infected macrophages. J. Immunol. 153:25682578.
103. Yu, K.,, C. Mitchell,, Y. Xing,, R. S. Magliozzo,, B. R. Bloom,, and J. Chan. 1999. Toxicity of nitrogen oxides and related oxidants on mycobacteria: M. tuberculosis is resistant to peroxynitrite anion. Tubercle Lung Dis. 79:191198.
104. Zerial, M.,, and H. McBride. 2001. Rab proteins as membrane organizers. Nat. Rev. Mol. Cell Biol. 2:107117.


Generic image for table
Table 1

Immune control of mycobacterial growth in the blood of tuberculosis patients and healthy volunteers

Citation: Chan J, Silver R, Kampmann B, Wallis R. 2005. Intracellular Models of Infection, p 437-450. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch27

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error