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Pathology of Tuberculosis: How the Pathology of Human Tuberculosis Informs and Directs Animal Models

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  • Authors: Randall J. Basaraba1, Robert L. Hunter2
  • Editors: William R. Jacobs Jr.3, Helen McShane4, Valerie Mizrahi5, Ian M. Orme6
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80524; 2: Department of Pathology and Laboratory Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030; 3: Howard Hughes Medical Institute, Albert Einstein School of Medicine, Bronx, NY 10461; 4: University of Oxford, Oxford OX3 7DQ, United Kingdom; 5: University of Cape Town, Rondebosch 7701, South Africa; 6: Colorado State University, Fort Collins, CO 80523
    • Source: microbiolspec June 2017 vol. 5 no. 3 doi:10.1128/microbiolspec.TBTB2-0029-2016
  • Received 30 July 2016 Accepted 19 April 2017 Published 09 June 2017
  • R. J. Basaraba, [email protected]
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  • Abstract:

    Tuberculosis (TB) is a chronic inflammatory disease caused by the pathogenic bacterium . A wide variety of host- and pathogen-associated variables influence the clinical manifestation of TB in different individuals within the human population. As a consequence, the characteristic granulomatous lesions that develop within the lung are heterogeneous in size and cellular composition. Due to the lack of appropriate tissues from human TB patients, a variety of animal models are used as surrogates to study the basic pathogenesis and to test experimental vaccines and new drug therapies. Few animal models mimic the clinical course and pathological response of seen in the naturally occurring disease in people. In particular, post-primary TB, which accounts for the majority of cases of active TB and is responsible for transmission between individuals via aerosol exposers, cannot be reproduced in animals and therefore cannot be adequately modeled experimentally. This article describes a new paradigm that explains the pathogenesis of post-primary TB in humans. This new evidence was derived from histological examination of tissues from patients with different stages of infection and that had not been treated with antimicrobial drugs. Gaining a better understanding of this unique stage of TB disease will lead to more effective treatment, diagnostic, and prevention strategies.

  • Citation: Basaraba R, Hunter R. 2017. Pathology of Tuberculosis: How the Pathology of Human Tuberculosis Informs and Directs Animal Models. Microbiol Spectrum 5(3):TBTB2-0029-2016. doi:10.1128/microbiolspec.TBTB2-0029-2016.

References

1. Nuermberger EL, Yoshimatsu T, Tyagi S, Bishai WR, Grosset JH. 2004. Paucibacillary tuberculosis in mice after prior aerosol immunization with Mycobacterium bovis BCG. Infect Immun 72:1065–1071 http://dx.doi.org/10.1128/IAI.72.2.1065-1071.2004.
2. Dannenberg AM Jr. 2006. Pathogenesis of Human Pulmonary Tuberculosis: Insights from the Rabbit Model, p 453. ASM Press, Washington, DC.
3. Hunter RL. 2011. Pathology of post primary tuberculosis of the lung: an illustrated critical review. Tuberculosis (Edinb) 91:497–509 http://dx.doi.org/10.1016/j.tube.2011.03.007.
4. Hunter RL, Actor JK, Hwang SA, Karev V, Jagannath C. 2014. Pathogenesis of post primary tuberculosis: immunity and hypersensitivity in the development of cavities. Ann Clin Lab Sci 44:365–387. [PubMed]
5. Hunter RL, Jagannath C, Actor JK. 2007. Pathology of postprimary tuberculosis in humans and mice: contradiction of long-held beliefs. Tuberculosis (Edinb) 87:267–278 http://dx.doi.org/10.1016/j.tube.2006.11.003.
6. Hunter RL. 2016. Tuberculosis as a three-act play: a new paradigm for the pathogenesis of pulmonary tuberculosis. Tuberculosis (Edinb) 97:8–17 http://dx.doi.org/10.1016/j.tube.2015.11.010.
7. Laennec R. 1821. A Treatise on Diseases of the Chest in Which They Are Described According to Their Anatomical Characters, and Their Diagnosis Established on a New Principle by Means of Acoustick Instruments, p 437. T&G Underwood, London, United Kingdom (reprinted 1979 by The Classics of Medicine Library, Birmingham, AL).
8. Dubos R, Dubos G. 1987. The White Plague. Tuberculosis, Man, and Society. Rutgers Univesity Press, New Brunswick, NJ.
9. Bennett JH. 1854. The Pathology and Treatment of Pulmonary Tuberculosis, p 180. Blanchard and Lea, Philadelphia, PA.
10. Virchow R. 1860. Cellular Pathology as Based upon Physiological and Pathological Histology, 2nd ed. John Churchill, London, United Kingdom (reprinted 1978 by The Classics of Medicine Library, Birmingham, AL).
11. Powell RD. 1876. On Consumption and on Certain Diseases of Lungs and Pleura, chapter 2, p 291. H.K. Lewis, London, United Kingdom.
12. Tyndale J. 1878. The Present Status of the Pathology of Consumption and Tuberculosis. Trow’s Printing and Bookbinding Co, New York, NY.
13. Cornil V, Ranvier L. 1880. Pathological histology of the respiratory apparatus, part III, section I, chapter II, p 394–445. In A Manual of Pathological Histology, Translated with Notes and Additions by EO Shakespeare and JHC Simms. Henry C Lea, Philadephia, PA.
14. Hamilton JD. 1883. On the Pathology of Bronchitis, Catarrhal Pneumonia. Tubercle and Allied Lesions of the Human Lung. Macmillan and Co, London, United Kingdom.
15. Hektoen L, Reisman D. 1901. A Text-Book of Pathology for the Use of Students and Practitoners of Medicine and Surgery, vol 2. W.B. Saunders & Company, London, United Kingdom.
16. Osler W, McCrae T. 1921. The Principles and Practice of Medicine, p 184–255. D. Appleton and Company, New York, NY.
17. Opie E, Aronson J. 1927. Tubercle bacilli in latent tuberculous lesions and in lung tissue without tuberculous lesions. Arch Pathol Lab Med 4:1–21.
18. Kayne GG, Pagel W, O’Shaughenessy L. 1939. Pulmonary Tuberculosis, Pathology, Diagnosis and Management. Oxford University Press, London, United Kingdom. [PubMed]
19. Rich A. 1951. The factors responsible for the characteristics of tuberculous lesions and symptoms, p 713. In The Pathogenesis of Tuberculosis, 2nd ed. Charles C Thomas, Springfield, IL.
20. Medlar EM. 1950. Pathogenetic concepts of tuberculosis. Am J Med 9:611–622 http://dx.doi.org/10.1016/0002-9343(50)90211-7.
21. Canetti G. 1955. The Tubercle Bacillus in the Pulmonary Lesion of Man. Histobacteriology and Its Bearing on the Therapy of Pulmonary Tuberculosis, p 226. Springer Publishing, New York, NY.
22. Gunn FD. 1961. Tuberculosis, p 243–263. In Anderson WAD (ed), Pathology, 4th ed. C.V. Mosby Company, St Louis, MO.
23. Pagel W. 1964. The morbid anatomy and histology of tuberculosis: an introduction in simple terms, p 36–63. In Pulmonary Tuberculosis, Bacteriology, Pathology, Diagnosis, Management, Epidemiology and Prevention. Oxford University Press, London, United Kingdom.
24. Aaron L, Saadoun D, Calatroni I, Launay O, Mémain N, Vincent V, Marchal G, Dupont B, Bouchaud O, Valeyre D, Lortholary O. 2004. Tuberculosis in HIV-infected patients: a comprehensive review. Clin Microbiol Infect 10:388–398 http://dx.doi.org/10.1111/j.1469-0691.2004.00758.x.
25. Mustafa T, Leversen NA, Sviland L, Wiker HG. 2014. Differential in vivo expression of mycobacterial antigens in Mycobacterium tuberculosis infected lungs and lymph node tissues. BMC Infect Dis 14:535 http://dx.doi.org/10.1186/1471-2334-14-535.
26. Hunter RL. 2011. On the pathogenesis of post primary tuberculosis: the role of bronchial obstruction in the pathogenesis of cavities. Tuberculosis (Edinb) 91(Suppl 1) :S6–S10 http://dx.doi.org/10.1016/j.tube.2011.10.003.
27. Sanders BM, Orme IM, Basaraba RJ. 2008. Immunopathology of tuberculosis. In Kaufmann SHE, Britton WJ (ed), Handbook of Tuberculosis: Immunology and Cell Biology. Wiley-VCH Verlag. Weinheim, Germany.
28. North RJ, Jung YJ. 2004. Immunity to tuberculosis. Annu Rev Immunol 22:599–623 http://dx.doi.org/10.1146/annurev.immunol.22.012703.104635. [PubMed]
29. Franzblau SG, DeGroote MA, Cho SH, Andries K, Nuermberger E, Orme IM, Mdluli K, Angulo-Barturen I, Dick T, Dartois V, Lenaerts AJ. 2012. Comprehensive analysis of methods used for the evaluation of compounds against Mycobacterium tuberculosis. Tuberculosis (Edinb) 92:453–488 http://dx.doi.org/10.1016/j.tube.2012.07.003.
30. Dannenberg AM Jr, Collins FM. 2001. Progressive pulmonary tuberculosis is not due to increasing numbers of viable bacilli in rabbits, mice and guinea pigs, but is due to a continuous host response to mycobacterial products. Tuberculosis (Edinb) 81:229–242 http://dx.doi.org/10.1054/tube.2001.0287.
31. Molina-Ruiz AM, Requena L. 2015. Foreign body granulomas. Dermatol Clin 33:497–523 http://dx.doi.org/10.1016/j.det.2015.03.014. [PubMed]
32. Medlar EM. 1955. The behavior of pulmonary tuberculous lesions: a pathological study. Am Rev Tuberc 71:1–244. [PubMed]
33. Dannenberg AM Jr. 1991. Delayed-type hypersensitivity and cell-mediated immunity in the pathogenesis of tuberculosis. Immunol Today 12:228–233 http://dx.doi.org/10.1016/0167-5699(91)90035-R. [PubMed]
34. Dannenberg AM Jr, Higuchi S. 1979. Chronic inflammation involving cellular hypersensitivity. Chest 75(Suppl) :265–266 http://dx.doi.org/10.1378/chest.75.2.265.
35. 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 (Edinb) 83:131–134 http://dx.doi.org/10.1016/S1472-9792(02)00079-3.
36. McMurray DN. 2001. Disease model: pulmonary tuberculosis. Trends Mol Med 7:135–137 http://dx.doi.org/10.1016/S1471-4914(00)01901-8.
37. Converse PJ, Dannenberg AM Jr, Shigenaga T, McMurray DN, Phalen SW, Stanford JL, Rook GA, Koru-Sengul T, Abbey H, Estep JE, Pitt ML. 1998. Pulmonary bovine-type tuberculosis in rabbits: bacillary virulence, inhaled dose effects, tuberculin sensitivity, and Mycobacterium vaccae immunotherapy. Clin Diagn Lab Immunol 5:871–881. [PubMed]
38. Dannenberg AM Jr. 2009. Liquefaction and cavity formation in pulmonary TB: a simple method in rabbit skin to test inhibitors. Tuberculosis (Edinb) 89:243–247 http://dx.doi.org/10.1016/j.tube.2009.05.006.
39. Converse PJ, Dannenberg AM Jr, Estep JE, Sugisaki K, Abe Y, Schofield BH, Pitt ML. 1996. Cavitary tuberculosis produced in rabbits by aerosolized virulent tubercle bacilli. Infect Immun 64:4776–4787. [PubMed]
40. Barclay WR, Ebert RH, Le Roy GV, Manthei RW, Roth LJ. 1953. Distribution and excretion of radioactive isoniazid in tuberculous patients. J Am Med Assoc 151:1384–1388. [PubMed]
41. Barclay WR, Ebert RH, Manthei RW, Roth LJ. 1953. Distribution of C14 labeled isoniazid in sensitive and resistant tubercle bacilli and in infected and uninfected tissues in tuberculous patients. Trans Annu Meet Natl Tuberc Assoc 49:192–195. [PubMed]
42. Coleman MT, Chen RY, Lee M, Lin PL, Dodd LE, Maiello P, Via LE, Kim Y, Marriner G, Dartois V, Scanga C, Janssen C, Wang J, Klein E, Cho SN, Barry CE III, Flynn JL. 2014. PET/CT imaging reveals a therapeutic response to oxazolidinones in macaques and humans with tuberculosis. Sci Transl Med 6:265ra167 http://dx.doi.org/10.1126/scitranslmed.3009500.
43. Dartois V. 2014. The path of anti-tuberculosis drugs: from blood to lesions to mycobacterial cells. Nat Rev Microbiol 12:159–167 http://dx.doi.org/10.1038/nrmicro3200. [PubMed]
44. Prideaux B, ElNaggar MS, Zimmerman M, Wiseman JM, Li X, Dartois V. 2015. Mass spectrometry imaging of levofloxacin distribution in TB-infected pulmonary lesions by MALDI-MSI and continuous liquid microjunction surface sampling. Int J Mass Spectrom 377:699–708 http://dx.doi.org/10.1016/j.ijms.2014.08.024.
45. Prideaux B, Via LE, Zimmerman MD, Eum S, Sarathy J, O’Brien P, Chen C, Kaya F, Weiner DM, Chen PY, Song T, Lee M, Shim TS, Cho JS, Kim W, Cho SN, Olivier KN, Barry CE III, Dartois V. 2015. The association between sterilizing activity and drug distribution into tuberculosis lesions. Nat Med 21:1223–1227 http://dx.doi.org/10.1038/nm.3937.
46. Subbian S, Tsenova L, Yang G, O’Brien P, Parsons S, Peixoto B, Taylor L, Fallows D, Kaplan G. 2011. Chronic pulmonary cavitary tuberculosis in rabbits: a failed host immune response. Open Biol 1:110016 http://dx.doi.org/10.1098/rsob.110016.
47. Hunter WA, Cundy T, Rabone D, Hofman PL, Harris M, Regan F, Robinson E, Cutfield WS. 2004. Insulin sensitivity in the offspring of women with type 1 and type 2 diabetes. Diabetes Care 27:1148–1152 http://dx.doi.org/10.2337/diacare.27.5.1148.
48. Klein EE. 1875. The Anatomy of the Lymphatic System. The Lung, vol 2. Smith, Elder and Co., London, United Kingdom.
49. Basaraba RJ, Smith EE, Shanley CA, Orme IM. 2006. Pulmonary lymphatics are primary sites of Mycobacterium tuberculosis infection in guinea pigs infected by aerosol. Infect Immun 74:5397–5401 http://dx.doi.org/10.1128/IAI.00332-06.
50. Rayner EL, Pearson GR, Hall GA, Basaraba RJ, Gleeson F, McIntyre A, Clark S, Williams A, Dennis MJ, Sharpe SA. 2013. Early lesions following aerosol infection of rhesus macaques ( Macaca mulatta) with Mycobacterium tuberculosis strain H37RV. J Comp Pathol 149:475–485 http://dx.doi.org/10.1016/j.jcpa.2013.05.005.
51. Klein EE. 1873. Contributions to the normal and pathological anatomy of the lymphatic system of the lungs. Proc R Soc Lond 22:133–145 http://dx.doi.org/10.1098/rspl.1873.0018.
52. Sanderson JB. 1867. Communicability of Tubercle by Innoculation. Report of the Medical Officer of the Privy Council. London, United Kingdom.
53. Basaraba RJ, Dailey DD, McFarland CT, Shanley CA, Smith EE, McMurray DN, Orme IM. 2006. Lymphadenitis as a major element of disease in the guinea pig model of tuberculosis. Tuberculosis (Edinb) 86:386–394 http://dx.doi.org/10.1016/j.tube.2005.11.003.
54. Lee P. 2015. Endobronchial tuberculosis. Indian J Tuberc 62:7–12 http://dx.doi.org/10.1016/j.ijtb.2015.02.002.
55. Peyron P, Vaubourgeix J, Poquet Y, Levillain F, Botanch C, Bardou F, Daffé M, Emile JF, Marchou B, Cardona PJ, de Chastellier C, Altare F. 2008. Foamy macrophages from tuberculous patients’ granulomas constitute a nutrient-rich reservoir for M. tuberculosis persistence. PLoS Pathog 4:e1000204 http://dx.doi.org/10.1371/journal.ppat.1000204.
56. Russell DG, Cardona PJ, Kim MJ, Allain S, Altare F. 2009. Foamy macrophages and the progression of the human tuberculosis granuloma. Nat Immunol 10:943–948 http://dx.doi.org/10.1038/ni.1781. [PubMed]
57. Mallat Z. 2014. Macrophages. Arterioscler Thromb Vasc Biol 34:2509–2519 http://dx.doi.org/10.1161/ATVBAHA.114.304794. [PubMed]
58. Basaraba RJ. 2008. Experimental tuberculosis: the role of comparative pathology in the discovery of improved tuberculosis treatment strategies. Tuberculosis (Edinb) 88(Suppl 1) :S35–S47 http://dx.doi.org/10.1016/S1472-9792(08)70035-0.
59. Irwin SM, Driver E, Lyon E, Schrupp C, Ryan G, Gonzalez-Juarrero M, Basaraba RJ, Nuermberger EL, Lenaerts AJ. 2015. Presence of multiple lesion types with vastly different microenvironments in C3HeB/FeJ mice following aerosol infection with Mycobacterium tuberculosis. Dis Model Mech 8:591–602 http://dx.doi.org/10.1242/dmm.019570.
60. Canetti G. 1956. Dynamic aspects of the pathology and bacteriology of tuberculous lesions. Am Rev Tuberc 74:13–21, discussion, 22–27. [PubMed]
61. Saunders BM. 2008. Immunopathology of tuberculosis, p 245–278. In Kaufmann SHE, Britton WJ (ed), Handbook of Tuberculosis: Immunology and Cell Biology. Wiley-VCH Verlag. Weinheim, Germany. [PubMed]
62. Ryan GJ, Hoff DR, Driver ER, Voskuil MI, Gonzalez-Juarrero M, Basaraba RJ, Crick DC, Spencer JS, Lenaerts AJ. 2010. Multiple M. tuberculosis phenotypes in mouse and guinea pig lung tissue revealed by a dual-staining approach. PLoS One 5:e11108 http://dx.doi.org/10.1371/journal.pone.0011108.
63. Ryan GJ, Shapiro HM, Lenaerts AJ. 2014. Improving acid-fast fluorescent staining for the detection of mycobacteria using a new nucleic acid staining approach. Tuberculosis (Edinb) 94:511–518 http://dx.doi.org/10.1016/j.tube.2014.07.004.
64. Bozza PT, Melo RCN, Bandeira-Melo C. 2007. Leukocyte lipid bodies regulation and function: contribution to allergy and host defense. Pharmacol Ther 113:30–49 http://dx.doi.org/10.1016/j.pharmthera.2006.06.006.
65. Kipnis A, Basaraba RJ, Turner J, Orme IM. 2003. Increased neutrophil influx but no impairment of protective immunity to tuberculosis in mice lacking the CD44 molecule. J Leukoc Biol 74:992–997 http://dx.doi.org/10.1189/jlb.0603301.
66. Ordway D, Palanisamy G, Henao-Tamayo M, Smith EE, Shanley C, Orme IM, Basaraba RJ. 2007. The cellular immune response to Mycobacterium tuberculosis infection in the guinea pig. J Immunol 179:2532–2541 http://dx.doi.org/10.4049/jimmunol.179.4.2532.
67. Tsai MC, Chakravarty S, Zhu G, Xu J, Tanaka K, Koch C, Tufariello J, Flynn J, Chan J. 2006. Characterization of the tuberculous granuloma in murine and human lungs: cellular composition and relative tissue oxygen tension. Cell Microbiol 8:218–232 http://dx.doi.org/10.1111/j.1462-5822.2005.00612.x.
68. Guo RF, Ward PA. 2002. Mediators and regulation of neutrophil accumulation in inflammatory responses in lung: insights from the IgG immune complex model. Free Radic Biol Med 33:303–310 http://dx.doi.org/10.1016/S0891-5849(02)00823-7.
69. Hu M, Miller EJ, Lin X, Simms HH. 2004. Transmigration across a lung epithelial monolayer delays apoptosis of polymorphonuclear leukocytes. Surgery 135:87–98 http://dx.doi.org/10.1016/S0039-6060(03)00347-7.
70. Zemans RL, Colgan SP, Downey GP. 2009. Transepithelial migration of neutrophils: mechanisms and implications for acute lung injury. Am J Respir Cell Mol Biol 40:519–535 http://dx.doi.org/10.1165/rcmb.2008-0348TR. [PubMed]
71. Hunter RL, Olsen M, Jagannath C, Actor JK. 2006. Trehalose 6,6′-dimycolate and lipid in the pathogenesis of caseating granulomas of tuberculosis in mice. Am J Pathol 168:1249–1261 http://dx.doi.org/10.2353/ajpath.2006.050848. [PubMed]
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2017-06-09
2021-04-14

Abstract:

Tuberculosis (TB) is a chronic inflammatory disease caused by the pathogenic bacterium . A wide variety of host- and pathogen-associated variables influence the clinical manifestation of TB in different individuals within the human population. As a consequence, the characteristic granulomatous lesions that develop within the lung are heterogeneous in size and cellular composition. Due to the lack of appropriate tissues from human TB patients, a variety of animal models are used as surrogates to study the basic pathogenesis and to test experimental vaccines and new drug therapies. Few animal models mimic the clinical course and pathological response of seen in the naturally occurring disease in people. In particular, post-primary TB, which accounts for the majority of cases of active TB and is responsible for transmission between individuals via aerosol exposers, cannot be reproduced in animals and therefore cannot be adequately modeled experimentally. This article describes a new paradigm that explains the pathogenesis of post-primary TB in humans. This new evidence was derived from histological examination of tissues from patients with different stages of infection and that had not been treated with antimicrobial drugs. Gaining a better understanding of this unique stage of TB disease will lead to more effective treatment, diagnostic, and prevention strategies.

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Pathology of Tuberculosis: How the Pathology of Human Tuberculosis Informs and Directs Animal Models
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Citation: Basaraba R, Hunter R. 2017. Pathology of tuberculosis: how the pathology of human tuberculosis informs and directs animal models. microbiolspec 5(3): doi:10.1128/microbiolspec.TBTB2-0029-2016
/content/microbiolspec/10.1128/microbiolspec.TBTB2-0029-2016.fig1
FIGURE 1
Well-delineated foci of granulomatous inflammation (granuloma) within the lung is a common manifestation of primary tuberculosis in humans and many laboratory animals. A low-magnification view of a primary lung granuloma from an -infected guinea pig has an area of central necrosis that is partially calcified . The wall of the lesion contains active lymphocytic and histiocytic inflammation and is well delineated from the surrounding normal lung parenchyma by a fibrous capsule that contains regenerative airway epithelium (black arrow). A higher-magnification view of the central dystrophic calcification (white arrow) shows residual tissue necrosis that harbors extracellular bacilli. Hematoxylin and eosin (H&E) stain.
microbiolspec/5/3/TBTB2-0029-2016-fig1_thmb.gif
microbiolspec/5/3/TBTB2-0029-2016-fig1.gif
Image of FIGURE 1

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FIGURE 1

Well-delineated foci of granulomatous inflammation (granuloma) within the lung is a common manifestation of primary tuberculosis in humans and many laboratory animals. A low-magnification view of a primary lung granuloma from an -infected guinea pig has an area of central necrosis that is partially calcified . The wall of the lesion contains active lymphocytic and histiocytic inflammation and is well delineated from the surrounding normal lung parenchyma by a fibrous capsule that contains regenerative airway epithelium (black arrow). A higher-magnification view of the central dystrophic calcification (white arrow) shows residual tissue necrosis that harbors extracellular bacilli. Hematoxylin and eosin (H&E) stain.

Source: microbiolspec June 2017 vol. 5 no. 3 doi:10.1128/microbiolspec.TBTB2-0029-2016
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/content/microbiolspec/10.1128/microbiolspec.TBTB2-0029-2016.fig2
FIGURE 2
An important manifestation of post-primary TB in humans that is not seen in many small animal models is the formation of thin wall cavities. Cavity formation (C) represents one of the most destructive manifestations of active tuberculosis in humans and non-human primates. The lung parenchyma is replaced by an open space that often contains necrotic cellular debris (N) and myriads of extracellular and intracellular bacilli that can be transmitted between individuals though aerosol spread. The wall of the cavity consists of mixed inflammation similar to primary granulomas and similarly is delineated from the more normal parenchyma by a fibrous capsule that impairs the penetration of antimicrobial drugs. H&E stain.
microbiolspec/5/3/TBTB2-0029-2016-fig2_thmb.gif
microbiolspec/5/3/TBTB2-0029-2016-fig2.gif
Image of FIGURE 2

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FIGURE 2

An important manifestation of post-primary TB in humans that is not seen in many small animal models is the formation of thin wall cavities. Cavity formation (C) represents one of the most destructive manifestations of active tuberculosis in humans and non-human primates. The lung parenchyma is replaced by an open space that often contains necrotic cellular debris (N) and myriads of extracellular and intracellular bacilli that can be transmitted between individuals though aerosol spread. The wall of the cavity consists of mixed inflammation similar to primary granulomas and similarly is delineated from the more normal parenchyma by a fibrous capsule that impairs the penetration of antimicrobial drugs. H&E stain.

Source: microbiolspec June 2017 vol. 5 no. 3 doi:10.1128/microbiolspec.TBTB2-0029-2016
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FIGURE 3
Cavity formation associated with post-primary TB is important in the transmission of bacilli between individuals due to the large numbers of extracellular and intracellular bacilli. High-magnification images of a cavitary lung lesion shown filling the lumen with necrotic cellular debris (white arrow). An acid-fast stain shows that bacilli within the necrotic debris are arranged in small clusters or as individuals (black arrow) and are mostly extracellular. The high numbers of bacilli within these lesions are important in the transmission of between individuals, especially when cavities communicate with lung airways. H&E stain.
microbiolspec/5/3/TBTB2-0029-2016-fig3_thmb.gif
microbiolspec/5/3/TBTB2-0029-2016-fig3.gif
Image of FIGURE 3

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FIGURE 3

Cavity formation associated with post-primary TB is important in the transmission of bacilli between individuals due to the large numbers of extracellular and intracellular bacilli. High-magnification images of a cavitary lung lesion shown filling the lumen with necrotic cellular debris (white arrow). An acid-fast stain shows that bacilli within the necrotic debris are arranged in small clusters or as individuals (black arrow) and are mostly extracellular. The high numbers of bacilli within these lesions are important in the transmission of between individuals, especially when cavities communicate with lung airways. H&E stain.

Source: microbiolspec June 2017 vol. 5 no. 3 doi:10.1128/microbiolspec.TBTB2-0029-2016
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FIGURE 4
Intrapulmonary spread of mixed inflammatory cells within the lung parenchyma results in an obstructive lobar pneumonia and is involved in the early pathogenesis of post-primary TB. In contrast to primary lesions, the filling of alveoli with mixed inflammatory cells, including foamy macrophages, in the absence of necrosis contributes to airway obstruction and the development of post-primary TB. H&E stain.
microbiolspec/5/3/TBTB2-0029-2016-fig4_thmb.gif
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FIGURE 4

Intrapulmonary spread of mixed inflammatory cells within the lung parenchyma results in an obstructive lobar pneumonia and is involved in the early pathogenesis of post-primary TB. In contrast to primary lesions, the filling of alveoli with mixed inflammatory cells, including foamy macrophages, in the absence of necrosis contributes to airway obstruction and the development of post-primary TB. H&E stain.

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FIGURE 5
Similarities in the time course of humans and animal models of TB demonstrating that pathology does not correlate with increased numbers of bacteria. A central problem in TB research is to explain why immunity to infection does not enable mice, guinea pigs, rabbits, or susceptible humans to resolve lung infection and thereby stop the development of disease.
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FIGURE 5

Similarities in the time course of humans and animal models of TB demonstrating that pathology does not correlate with increased numbers of bacteria. A central problem in TB research is to explain why immunity to infection does not enable mice, guinea pigs, rabbits, or susceptible humans to resolve lung infection and thereby stop the development of disease.

Source: microbiolspec June 2017 vol. 5 no. 3 doi:10.1128/microbiolspec.TBTB2-0029-2016
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