Chapter 16 : Infections

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

Preview this chapter:
Zoom in

Infections, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555818104/9781555811594_Chap16-1.gif /docserver/preview/fulltext/10.1128/9781555818104/9781555811594_Chap16-2.gif


The host's cellular immune response appears to determine the fate of the organisms escaping the dormant state. It is the depletion of CD4 cells which leads to the increased rate of reactivation of latent tuberculosis infection in patients dually infected with human immunodeficiency virus (HIV) and tuberculosis. This chapter discusses mechanisms responsible for these phenomena and describes the methods of studying dormancy. Tuberculosis is a chronic infection caused by . predominantly causes disease in the lungs, although it can affect any organ in the body. The infected macrophages spread through the lymphatic channels to regional lymph nodes and then metastasize throughout the body. The interactions of macrophages, lymphocytes, and the organism result in regulation of the immune response in tuberculosis. One study of human alveolar macrophages failed to demonstrate either production of nitric oxide synthase mRNA or nitrous oxide following stimulation of the macrophages by mycobacteria. The human immune response to mycobacteria is decidedly a TH1-like response and is characteristic of the cellular immune response to intracellular pathogens. The adaptive process may then involve a switchover to a reduced metabolic state or to a spore-like state that becomes insusceptible to drug action. Investigation of mycobacterial cells which pass from an actively multiplying state to a low-metabolic nonmultiplying state identified a switch in metabolism to the glyoxalate cycle, which permits adaptation to the usually lethal effects of anaerobiosis.

Citation: Trucksis M. 2000. Infections, p 327-337. In Nataro J, Blaser M, Cunningham-Rundles S (ed), Persistent Bacterial Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818104.ch16
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of FIGURE 1

Model of the cellular immune response to tuberculosis. The cellular immune response to tuberculosis infection involves a complex network of bidirectional cellular and cytokine interactions. The dashed arrows and mediators shown in gray represent inhibitory pathways. TNF-α, tumor necrosis factor alpha; MΦ, macrophage; CTL, cytotoxic T lymphocyte.

Citation: Trucksis M. 2000. Infections, p 327-337. In Nataro J, Blaser M, Cunningham-Rundles S (ed), Persistent Bacterial Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818104.ch16
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Adams, L. B.,, C. M. Mason,, J. K. Rolls,, D . Scollard,, J. L. Krahenbuhl,, and S. Nelson. 1995. Exacerbation of acute and chronic murine tuberculosis by administration of a tumor necrosis factor receptor-expressing adenovirus. J. Infect. Dis. 171: 400 405.
2. Aston, C.,, W. N. Rom,, A. T. Talbot,, and J. Reibman. 1998. Early inhibition of mycobacterial growth by human alveolar macrophages is not due to nitric oxide. Atn.f. Respir. Crit. Care Med. 157: 1943 1950.
3. Berton, G.,, C. Laudanna,, C. Sorio,, and F. Rossi. 1992. Generation of signals activating neutrophil functions by leukocyte integrins: LFA-1 and gp 150/95, but not CR3, are able to stimulate the respiratory burst o f human neutrophils. J. Cell Biol 116: 1007 1017.
4. Bloom , B. R.,, and C. J. L. Murray. 1992. Tuberculosis: commentary on a reemergent killer. Science 257: 1055 1064.
5. Boom , W. H. 1996. The role of T-cell subsets in Mycobacterium tuberculosis infection. Infect. Agents Dis. 5: 73 81.
6. Brennan, P. J. 1997. Tuberculosis in the context of emerging and reemerging diseases. FEMS Immunol Med. Microbiol 18: 263 269.
7. Brown, D. H.,, B. A. Miles,, and B. S. Zwil-ling. 1995. Growth of Mycobacterium tuberculosis in BCG-resistant and -susceptible mice: estabhshment of latency and reactivation. Infect. Immun. 63: 2243 2247.
8. 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: 736 740.
9. Comstock, G. W.,, and S. F. Woolpert. 1972. Preventive treatment of untreated, nonactive tuberculosis in an Eskimo population. Arch. Environ. Health 25: 333 337.
10. Cunningham, A. F.,, and C. L. Spreadbury. 1998. Mycobacterial stationary phase induced by l ow oxygen tension: cell wall thickening and l o calization o f the 16-kilodalton a-crystallin homology. J. Bacteriol 180: 801 808.
11. Dannenberg, A. M.,, and G. A. W. Rook,. 1994. Pathogenesis of pulmonary tuberculosis: an interplay of tissue-damaging and macrophage-activating immune responses—dual mechanisms that control bacillary multiplication, p. 459 483. In B. R. Bloom (ed.), Tuberculosis: Pathogenesis, Protection, and Control. American Society for Microbiology, Washington, D.C.
12. DeMaio , J.,, Y. Zhang ,, C. Ko ,, D. B. Young,, and W. R. Bishai. 1996. A stationary-phase stress-response sigma factor from Mycobacterium tuberculosis. Proc. Natl Acad. Sci. USA 93: 2790 2794.
13. DeWit, D.,, M. Wootton ,, J. Dhillon ,, and D . A. Mitchison. 1995. The bacterial D N A content of mouse organs in the Cornell model of dormant tuberculosis. Tuber. Lung Dis. 76: 555 562.
14. Dockrell, H. M.,, S. K. Young ,, K. Britton,, P. J. Brennan,, B. Rivoire ,, M. F. R. Waters,, S. B. Lucas,, F. Shahid,, M. Dojki,, T. J. Chiang,, Q. Ehsan,, K. P. W. J. McAdam ,, and R. Hussain. 1996. Induction of Thl cytokine responses by mycobacterial antigens in leprosy. Infect. Immun. 64: 4385 4389.
15. Dolin , P. J.,, M. C. Raviglione ,, and A. Kochi. 1994. Global tuberculosis incidence and mortality during 1990-2000. Bull W. H. O. 72: 213 220.
16. Downi g , J. F.,, R. Pasula,, J. R. Wright,, H. L. Twiggffl,, and W. J. Martin II. 1995. Surfactant protein A promotes attachment o f Mycobacterium tuberculosis to alveolar macrophages during infection with human immunodeficiency virus. Proc. Natl Acad. Sci. USA 92: 4848 4852.
17. Ehlers, M. R. W.,, and M. DafFe. 1998. Interactions between Mycobacterium tuberculosis and host cells: are mycobacterial sugars the key? Trends Microbiol 6: 328 335.
18. Ellner, J. J. 1997. Review: the immune response in human tuberculosis—implications for tuberculosis control. J. Infect. Dis. 176: 1351 1359.
19. Flynn, J. L.,, C. A. Scanga,, K. E. Tanaka,, and J. Chan. 1998. Effects of aminoguanidine on latent murine tuberculosis. J. Immunol 160: 1796 1803.
20. Gelber, R. H., 1995. Leprosy (Hansen's disease), p. 2243 2250. In G. L. Mandell,, J. E. Bennett,, and R. Dolin (ed.), Principles and Practice of Infectious Diseases. Churchill Livingstone, New York, N.Y.
21. Gordon, A. H.,, P. D'Arcy Hart,, and M. R. Young. 1980. Ammonia inhibits phagosome-lysosome fusion in macrophages. Nature 286: 79 80.
22. Hirsch, C. S.,, J. J. Ellner,, D. G. Russell,, and E. A. Rich. 1994. Complement receptor-mediated uptake and tumor necrosis factor-a-mediated growth inhibition of Mycobacterium tuberculosis by human alveolar macrophages. J. Immunol. 152: 743 753.
23. Hu, Y. M.,, P. D. Butcher,, K. Sole,, D. A. Mitchison,, and A. R. M. Coates. 1998. Protein synthesis is shut down in dormant Mycobacterium tuberculosis and is reversed by oxygen or heat shock. FEMS Microbiol Lett. 158: 139 145.
24. Kaplan, G. 1994. Cytokine regulation of disease progression in leprosy and tuberculosis. Immunobiology 191: 564 568.
25. Kaplan, G.,, and V. H. Freedman. 1996. The role o f cytokines in the immune response to tuberculosis. Res. Immunol. 147: 565 572.
26. Khomenko , A. G. 1987. The variability of Mycobacterium tuberculosis in patients with cavitary pulmonary tuberculosis in the course of chemotherapy. Tubercle 68: 243 253.
27. Korovessis, P.,, E. Papadaki,, M. Repanti,, and M. Stamatakis. 1995. Latent solitary tuberculous psoas abscess 52 years after healed thoracolumbar tuberculous spondylitis. Spine 15: 1709 1712.
28. Lygren, S. T.,, O. Closs,, H. Bercouvier,, and L. G. Wayne. 1986. Catalases, peroxidases, and superoxide dismutase in Mycobacterium leprae and other mycobacteria studied by cross immunoelectrophoresis and polyacrylamide gel electrophoresis. Infect. Immun. 54: 666 671.
29. Marth, T.,, and B. L. Kelsall. 1997. Regulation of interleukin-12 by complement receptor 3 signaling. J. Exp. Med. 185: 1987 1995.
30. McCune, R. M.,, F. M. Feldmann,, H. P. Lambert,, and W. Mc Dermott. 1966. Microbial persistence. I. The capacity of tubercle bacilli to survive sterilization in mouse tissues. J. Exp. Med. 123: 445 468.
31. McCune, R. M.,, F. M. Feldmann,, and W. Mc Dermott. 1966. Microbial persistence. II. Characteristics of the sterile state of tubercle bacilli. J. Exp. Med. 123: 469 486.
32. Mehlen, P.,, J. Briolay,, L. Smith,, C. Diaz-Latoud,, N. Fabre,, D. Pauli,, and A. P. Arrigo. 1993. Analysis of the resistance to heat and hydrogen peroxide stresses in COS cells transiendy expressing wild type or deletion mutants o f the Drosophila 27-kDa heat-shock protein. Eur. J. Biochem. 215: 277 284.
33. Molloy, A.,, G. Gaudernack,, W. R. Levis,, Z. A. Cohn,, and G. Kaplan. 1990. Suppression of T-cell proliferation by Mycobacterium leprae and its products: the role of lipopolysaccharide. Proc. Natl Acad. Sci. USA 87: 973 977.
34. Neill, M. A.,, and S. J. Klebanoff. 1988. The effect of phenolic glycolipid-1 from Mycobacterium leprae on the antimicrobial activity of human macrophages./ Exp. Med. 167: 30 42.
35. Nicholson , S.,, M. G. Bonecini-Almeida ,, J. R. LapaeSilva,, C. Nathan,, Q. W. Xie ,, R. Mumford,, J. R. Weidner,, J. Calaycay,, J. Geng,, and N. Boechat. 1996. Inducible nitric oxide synthase in pulmonary alveolar macrophages from patients with tuberculosis. J. Exp. Med. 183: 2293 2302.
36. Orme, I. M. 1988. A mouse model of the recrudescence of latent tuberculosis in the elderly. Am. Rev. Respir. Dis. 137: 716 718.
37. Phyu, S.,, T. Mustafa,, T. Hofstad,, R. Nilsen,, R. Fosse,, and G. Bjune. 1998. A mouse model for latent tuberculosis. Scand. J. Infect. Dis. 30: 59 68.
38. Rook , G. A.,, W. J. Taverne,, C. Leveton,, and J. Steele. 1987. The role of gamma-interferon, vitamin D 3 metabolites and tumor necrosis factor in the pathogenesis o f tuberculosis. Immunology 62: 229 234 .
39. Sathish, M.,, and T. M. Shinnick. 1994. Identification of genes involved in resistance of mycobacteria to killing by macrophages. Ann. N. Y. Acad. Sci. 730: 26 36.
40. Schlesinger, L. S. 1993. Macrophage phagocytosis o f virulent but not attenuated strains o f Mycobacterium tuberculosis is mediated by mannose receptors in addition to complement receptors. J. Immunol 150: 2920 2930.
41. Schlesinger, L. S.,, C. G. Bellinger-Kawahara,, N. R. Payne ,, and M. A. Horwitz. 1990. Phagocytosis of Mycobacterium tuberculosis is mediated by human monocyte complement receptors and complement component C3. J. Immunol 144: 2771 2780.
42. Schorey, J. S.,, M. C. Carroll,, and E. J. Brown. 1997. A macrophage invasion mechanism of pathogenic mycobacteria. Science 277: 1091 1093.
43. Schorey, J. S.,, Q. Li,, D. W. McCourt,, M. Bong-Mastek,, J. E. Clark-Curtiss,, T. L. Ratliff,, and E. J. Brown. 1995. A Mycobacterium leprae gene encoding a fibronectin binding protein is used for efficient invasion of epithelial cells and Schwann cells. Infect. Immun. 63: 2652 2657'.
44. Shinnick, T. M.,, H. King,, and F. D. Quinn. 1995. Molecular biology, virulence and pathogenicity of mycobacteria. Am. J. Med. Sci. 309: 92 98 .
45. Stanford, J. L. 1987. Much's granules revisited. Tubercle 68: 241 242.
46. Stokes, R. W.,, I. D. Haidl,, W. A. JefFeries,, and D. P. Speert. 1993. Mycobacteria-macrophage interactions: macrophage phenotype determines the nonopsonic binding of Mycobacterium tuberculosis to murine macrophages. J. Immunol. 151: 7067 7076.
47. 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 pro ton-ATPase. Science 263: 678 681 .
48. Vandiviere, H. M.,, W. E. Loring,, I. Melvin,, S. Willis, et al. 1956. The treated pulmonary lesion and its tubercle bacillus. II. The death and resurrection. Am.J. Med. Sci. 232: 30 37.
49. Wallis, R. S.,, M. Perkins,, M. Phillips,, M. Joloba ,, B. Demchuk ,, A. Namale ,, J. L. Johnson,, D. Williams,, K. Wolski,, L. Teixeira,, R. Dietze ,, R. D. Mugerwa,, K. Eisenach,, and J. J. Ellner. 1998. Induction of the antigen 85 complex of Mycobacterium tuberculosis in sputum: a determinant of outcome in pulmonary tuberculosis treatment. J. Infect. Dis. 178: 1115 1121.
50. Wayne, L. G. 1976. Dynamics of submerged growth of Mycobacterium tuberculosis under aerobic and rmcroaerophilic conditions. Am. Rev. Respir. Dis. 114: 807 811.
51. Wayne, L. G. 1994. Dormancy of Mycobacterium tuberculosis and latency o f disease. Eur.J. Clin. Microbiol. Infect. Dis. 13: 908 914.
52. Wayne, L. G.,, and L. G. Hayes. 1996. An in vitro model for sequential study of shiftdown of Mycobacterium tuberculosis through two stages of nonreplicating persistence. Infect. Immun. 64: 2062 2069.
53. Wayne, L. G.,, and K. Y. Lin. 1982. Glyoxylate metabolism and adaptation of Mycobacterium tuberculosis to survival under anaerobic conditions. Infect. Immun. 37: 1042 1049.
54. Wayne, L. G.,, and D. Salkin. 1956. The bacteriology of resected tuberculous pulmonary lesions. I. The effect of interval between reversal of infectiousness and subsequent surgery. Am. Rev. Tuber. 74: 376 387.
55. Wayne, L. G.,, and H. A. Sramek. 1994. Metronidazole is bactericidal to dormant cells o f Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 38: 2054 2058.
56. Weiles, B.,, T. H. M. Ottenhoff,, T. M. Steenwijk,, K. L. M. C. Franken,, R. R. P. DeVries ,, and J. A. M. Langerman. 1997. Increased intracellular survival of Mycobacterium smegmatis containing the Mycobacterium leprae thioredoxin- thioredoxin reductase gene. Infect. Immun. 65: 2537 2541.
57. Wright, S. D.,, and S. C. Silverstein. 1983. Receptors for C3b and C3bi promote phagocytosis but not the release of toxic oxygen from human phagocytes. J. Exp. Med. 158: 2016 2023.
58. Yamamura, M.,, K. Uyemura ,, R. J. Deans,, K. Weinberg,, T. H. Rea ,, B. R. Bloom ,, and R. L. Modlin. 1991. Defining protective responses to pathogens: cytokine profiles in leprosy patients. Science 254: 277 279.
59. Yuan, Y.,, D. D. Crane,, and C. E. Barry III. 1996. Stationary phase-associated protein expression in Mycobacterium tuberculosis: function of the mycobacterial a-crystallin homolog. J. Bacteriol. 178: 4484 4492.

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