Frontiers in Biology

, Volume 10, Issue 3, pp 252–261 | Cite as

The bacterial and host factors associated with extrapulmonary dissemination of Mycobacterium tuberculosis

  • Dong Yang
  • Ying KongEmail author


With high morbidity and mortality worldwide, tuberculosis (TB) is still an important public health threat. The majority of human TB cases are caused by Mycobacterium tuberculosis. Although pulmonary TB is the most common presentation, M. tuberculosis can disseminate into other organs and causes extrapulmonary TB (EPTB). The dissemination of bacteria from the initial site of infection to other organs can lead to fatal diseases, such as miliary and meningeal TB. Thoroughly understanding the mechanisms and pathways of dissemination would develop therapies to prevent the lethal prognosis of EPTB (miliary and meningeal TB) and vaccines to promote the development of adaptive immunity. This review focuses on risk factors of EPTB, bacterial and host genes involved in EPTB, and potential mechanisms of M. tuberculosis extrapulmonary dissemination.


Mycobacterium tuberculosis extrapulmonary dissemination risk factors bacterial genes host genes 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adams D O (1976). The granulomatous inflammatory response. A review. Am J Pathol, 84(1): 164–192Google Scholar
  2. Alvarado-Esquivel C, García-Corral N, Carrero-Dominguez D, Enciso-Moreno J A, Gurrola-Morales T, Portillo-Gómez L, Rossau R, Mijs W (2009). Molecular analysis of Mycobacterium isolates from extrapulmonary specimens obtained from patients in Mexico. BMC Clin Pathol, 9(1): 1PubMedCentralPubMedGoogle Scholar
  3. American Thoracic Society, Infectious Diseases Society of America (2000). Diagnostic standards and classification of tuberculosis in adults and children. Am J Respir Crit Care Med, 161(4 Pt 1): 1376–1395Google Scholar
  4. Antonucci G, Girardi E, Raviglione MC, Ippolito G (1995). Risk factors for tuberculosis in HIV-infected persons. A prospective cohort study. The Gruppo Italiano di Studio Tubercolosi e AIDS (GISTA). JAMA, 274(2): 143–148PubMedGoogle Scholar
  5. Arias M, Zabaleta J, Rodríguez J I, Rojas M, París S C, García L F (1997). Failure to induce nitric oxide production by human monocyte-derived macrophages. Manipulation of biochemical pathways. Allergol Immunopathol (Madr), 25(6): 280–288Google Scholar
  6. Arruda S, Bomfim G, Knights R, Huima-Byron T, Riley L W (1993). Cloning of an M. tuberculosis DNA fragment associated with entry and survival inside cells. Science, 261(5127): 1454–1457PubMedGoogle Scholar
  7. Asghar R J, Pratt R H, Kammerer J S, Navin T R (2008). Tuberculosis in South Asians living in the United States, 1993–2004. Arch Intern Med, 168(9): 936–942PubMedGoogle Scholar
  8. Barnes P F, Barrows S A (1993). Tuberculosis in the 1990s. Ann Intern Med, 119(5): 400–410PubMedGoogle Scholar
  9. Barrios-Payán J, Saqui-Salces M, Jeyanathan M, Alcántara-Vazquez A, Castañon-Arreola M, Rook G, Hernandez-Pando R (2012). Extrapulmonary locations of Mycobacterium tuberculosis DNA during latent infection. J Infect Dis, 206(8): 1194–1205PubMedGoogle Scholar
  10. Bates M N, Khalakdina A, Pai M, Chang L, Lessa F, Smith K R (2007). Risk of tuberculosis from exposure to tobacco smoke: a systematic review and meta-analysis. Arch Intern Med, 167(4): 335–342PubMedGoogle Scholar
  11. Be N A, Lamichhane G, Grosset J, Tyagi S, Cheng Q J, Kim K S, Bishai W R, Jain S K (2008). Murine model to study the invasion and survival of Mycobacterium tuberculosis in the central nervous system. J Infect Dis, 198(10): 1520–1528PubMedGoogle Scholar
  12. Bekker L G, Moreira A L, Bergtold A, Freeman S, Ryffel B, Kaplan G (2000). Immunopathologic effects of tumor necrosis factor alpha in murine mycobacterial infection are dose dependent. Infect Immun, 68(12): 6954–6961PubMedCentralPubMedGoogle Scholar
  13. Boom WH, Canaday D H, Fulton S A, Gehring A J, Rojas R E, Torres M (2003). Human immunity to M. tuberculosis: T cell subsets and antigen processing. Tuberculosis (Edinb), 83(1–3): 98–106Google Scholar
  14. Bouley D M, Ghori N, Mercer K L, Falkow S, Ramakrishnan L (2001). Dynamic nature of host-pathogen interactions in Mycobacterium marinum granulomas. Infect Immun, 69(12): 7820–7831PubMedCentralPubMedGoogle Scholar
  15. Brewer T F, Heymann S J (2005). Long time due: reducing tuberculosis mortality in the 21st century. Arch Med Res, 36(6): 617–621PubMedGoogle Scholar
  16. Cailhol J, Decludt B, Che D (2005). Sociodemographic factors that contribute to the development of extrapulmonary tuberculosis were identified. J Clin Epidemiol, 58(10): 1066–1071PubMedGoogle Scholar
  17. Campbell G R, Spector S A (2012). Vitamin D inhibits human immunodeficiency virus type 1 and Mycobacterium tuberculosis infection in macrophages through the induction of autophagy. PLoS Pathog, 8(5): e1002689PubMedCentralPubMedGoogle Scholar
  18. Camus J C, Pryor MJ, Médigue C, Cole S T (2002). Re-annotation of the genome sequence of Mycobacterium tuberculosis H37Rv. Microbiology, 148(Pt 10): 2967–2973PubMedGoogle Scholar
  19. Caruso A M, Serbina N, Klein E, Triebold K, Bloom B R, Flynn J L (1999). Mice deficient in CD4 T cells have only transiently diminished levels of IFN-gamma, yet succumb to tuberculosis. J Immunol, 162(9): 5407–5416PubMedGoogle Scholar
  20. Casali N, Riley L W (2007). A phylogenomic analysis of the Actinomycetales mce operons. BMC Genomics, 8(1): 60PubMedCentralPubMedGoogle Scholar
  21. Castro-Garza J, King C H, Swords W E, Quinn F D (2002). Demonstration of spread by Mycobacterium tuberculosis bacilli in A549 epithelial cell monolayers. FEMS Microbiol Lett, 212(2): 145–149PubMedGoogle Scholar
  22. Centers for Disease Control and Prevention (CDC) (2008). Trends in tuberculosis—United States, 2007. MMWR Morb Mortal Wkly Rep, 57(11): 281–285Google Scholar
  23. Chan-Yeung M, Noertjojo K, Chan S L, Tam C M (2002). Sex differences in tuberculosis in Hong Kong. Int J Tuberc Lung Dis, 6(1): 11–18PubMedGoogle Scholar
  24. Chang J C, Harik N S, Liao R P, Sherman D R (2007). Identification of Mycobacterial genes that alter growth and pathology in macrophages and in mice. J Infect Dis, 196(5): 788–795PubMedGoogle Scholar
  25. Chawla M, Parikh P, Saxena A, Munshi M, Mehta M, Mai D, Srivastava A K, Narasimhulu K V, Redding K E, Vashi N, Kumar D, Steyn A J, Singh A (2012). Mycobacterium tuberculosis WhiB4 regulates oxidative stress response to modulate survival and dissemination in vivo. Mol Microbiol, 85(6): 1148–1165PubMedCentralPubMedGoogle Scholar
  26. Chiang C Y, Slama K, Enarson D A (2007). Associations between tobacco and tuberculosis. Int J Tuberc Lung Dis, 11(3): 258–262PubMedGoogle Scholar
  27. Cirillo S L, Subbian S, Chen B, Weisbrod T R, Jacobs WR Jr, Cirillo J D (2009). Protection of Mycobacterium tuberculosis from reactive oxygen species conferred by the mel2 locus impacts persistence and dissemination. Infect Immun, 77(6): 2557–2567PubMedCentralPubMedGoogle Scholar
  28. Clay H, Davis J M, Beery D, Huttenlocher A, Lyons S E, Ramakrishnan L (2007). Dichotomous role of the macrophage in early Mycobacterium marinum infection of the zebrafish. Cell Host Microbe, 2(1): 29–39PubMedCentralPubMedGoogle Scholar
  29. Cole S T (2002). Comparative and functional genomics of the Mycobacterium tuberculosis complex. Microbiology, 148(Pt 10): 2919–2928PubMedGoogle Scholar
  30. Cole S T, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon S V, Eiglmeier K, Gas S, Barry C E 3rd, Tekaia F, Badcock K, Basham D, Brown D, Chillingworth T, Connor R, Davies R, Devlin K, Feltwell T, Gentles S, Hamlin N, Holroyd S, Hornsby T, Jagels K, Krogh A, McLean J, Moule S, Murphy L, Oliver K, Osborne J, Quail M A, Rajandream M A, Rogers J, Rutter S, Seeger K, Skelton J, Squares R, Squares S, Sulston J E, Taylor K, Whitehead S, Barrell B G (1998). Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature, 393(6685): 537–544PubMedGoogle Scholar
  31. Cooper A M, Dalton D K, Stewart T A, Griffin J P, Russell D G, Orme I M (1993). Disseminated tuberculosis in interferon gamma genedisrupted mice. J Exp Med, 178(6): 2243–2247PubMedGoogle Scholar
  32. Dannenberg A M Jr (1989). Immune mechanisms in the pathogenesis of pulmonary tuberculosis. Rev Infect Dis, 11(Suppl 2): S369–S378PubMedGoogle Scholar
  33. Davis J M, Ramakrishnan L (2009). The role of the granuloma in expansion and dissemination of early tuberculous infection. Cell, 136(1): 37–49PubMedCentralPubMedGoogle Scholar
  34. Davis N K, Chater K F (1992). The Streptomyces coelicolor whiB gene encodes a small transcription factor-like protein dispensable for growth but essential for sporulation. Mol Gen Genet, 232(3): 351–358PubMedGoogle Scholar
  35. de Jong R, Altare F, Haagen I A, Elferink D G, Boer T, van Breda Vriesman P J, Kabel P J, Draaisma J M, van Dissel J T, Kroon F P, Casanova J L, Ottenhoff T H (1998). Severe mycobacterial and Salmonella infections in interleukin-12 receptor-deficient patients. Science, 280(5368): 1435–1438PubMedGoogle Scholar
  36. Dobos K M, Spotts E A, Quinn F D, King C H (2000). Necrosis of lung epithelial cells during infection with Mycobacterium tuberculosis is preceded by cell permeation. Infect Immun, 68(11): 6300–6310PubMedCentralPubMedGoogle Scholar
  37. Edwards D, Kirkpatrick C H (1986). The immunology of mycobacterial diseases. Am Rev Respir Dis, 134(5): 1062–1071PubMedGoogle Scholar
  38. Farer L S, Lowell A M, Meador M P (1979). Extrapulmonary tuberculosis in the United States. Am J Epidemiol, 109(2): 205–217PubMedGoogle Scholar
  39. Fenton M J, Vermeulen MW (1996). Immunopathology of tuberculosis: roles of macrophages and monocytes. Infect Immun, 64(3): 683–690PubMedCentralPubMedGoogle Scholar
  40. Fernando S L, Saunders B M, Sluyter R, Skarratt K K, Goldberg H, Marks G B, Wiley J S, Britton W J (2007). A polymorphism in the P2X7 gene increases susceptibility to extrapulmonary tuberculosis. Am J Respir Crit Care Med, 175(4): 360–366PubMedGoogle Scholar
  41. Fiske C T, Griffin M R, Erin H, Warkentin J, Lisa K, Arbogast P G, Sterling T R (2010). Black race, sex, and extrapulmonary tuberculosis risk: an observational study. BMC Infect Dis, 10(1): 16PubMedCentralPubMedGoogle Scholar
  42. Flynn J L, Chan J (2001). Immunology of tuberculosis. Annu Rev Immunol, 19(1): 93–129PubMedGoogle Scholar
  43. Forssbohm M, Zwahlen M, Loddenkemper R, Rieder H L (2008). Demographic characteristics of patients with extrapulmonary tuberculosis in Germany. Eur Respir J, 31(1): 99–105PubMedGoogle Scholar
  44. Fortune S M, Solache A, Jaeger A, Hill P J, Belisle J T, Bloom B R, Rubin E J, Ernst J D (2004). Mycobacterium tuberculosis inhibits macrophage responses to IFN-gamma through myeloid differentiation factor 88-dependent and-independent mechanisms. J Immunol, 172(10): 6272–6280PubMedGoogle Scholar
  45. Gioffré A, Infante E, Aguilar D, Santangelo M P, Klepp L, Amadio A, Meikle V, Etchechoury I, Romano M I, Cataldi A, Hernández R P, Bigi F (2005). Mutation in mce operons attenuates Mycobacterium tuberculosis virulence. Microbes Infect, 7(3): 325–334PubMedGoogle Scholar
  46. Gombart A F, Borregaard N, Koeffler H P (2005). Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1, 25-dihydroxyvitamin D3. FASEB J, 19(9): 1067–1077PubMedGoogle Scholar
  47. Gonzalez O Y, Adams G, Teeter L D, Bui T T, Musser J M, Graviss E A (2003). Extra-pulmonary manifestations in a large metropolitan area with a low incidence of tuberculosis. Int J Tuberc Lung Dis, 7(12): 1178–1185PubMedGoogle Scholar
  48. Gordon A H, Hart P D, Young M R (1980). Ammonia inhibits phagosome-lysosome fusion in macrophages. Nature, 286(5768): 79–80PubMedGoogle Scholar
  49. Goren M B, D’Arcy Hart P, Young M R, Armstrong J A (1976). Prevention of phagosome-lysosome fusion in cultured macrophages by sulfatides of Mycobacterium tuberculosis. Proc Natl Acad Sci USA, 73(7): 2510–2514PubMedCentralPubMedGoogle Scholar
  50. Haas D W, Des Prez R M (1994). Tuberculosis and acquired immunodeficiency syndrome: a historical perspective on recent developments. Am J Med, 96(5): 439–450PubMedGoogle Scholar
  51. Harris S S (2006). Vitamin D and African Americans. J Nutr, 136(4): 1126–1129PubMedGoogle Scholar
  52. Hart P D, Young M R, Jordan M M, Perkins W J, Geisow M J (1983). Chemical inhibitors of phagosome-lysosome fusion in cultured macrophages also inhibit saltatory lysosomal movements. A combined microscopic and computer study. J Exp Med, 158(2): 477–492PubMedGoogle Scholar
  53. Henao M I, Montes C, París S C, García L F (2006). Cytokine gene polymorphisms in Colombian patients with different clinical presentations of tuberculosis. Tuberculosis (Edinb), 86(1): 11–19Google Scholar
  54. Henkle E, Winthrop K L (2015). Nontuberculous mycobacteria infections in immunosuppressed hosts. Clin Chest Med, 36(1): 91–99PubMedGoogle Scholar
  55. Hoal-Van Helden E G, Epstein J, Victor T C, Hon D, Lewis L A, Beyers N, Zurakowski D, Ezekowitz A B, Van Helden P D (1999). Mannosebinding protein B allele confers protection against tuberculous meningitis. Pediatr Res, 45(4 Pt 1): 459–464PubMedGoogle Scholar
  56. Holmes C B, Hausler H, Nunn P (1998). A review of sex differences in the epidemiology of tuberculosis. Int J Tuberc Lung Dis, 2(2): 96–104PubMedGoogle Scholar
  57. Hopewell P (1994). Overview of Clinical Tuberculosis. In: Barry B (ed.). Tuberculosis: Pathogenesis, Protection and Control. ASM Press, Washington, DC. pp. 25–46Google Scholar
  58. Hsu T, Hingley-Wilson S M, Chen B, Chen M, Dai A Z, Morin P M, Marks C B, Padiyar J, Goulding C, Gingery M, Eisenberg D, Russell R G, Derrick S C, Collins F M, Morris S L, King C H, Jacobs W R Jr (2003). The primary mechanism of attenuation of bacillus Calmette-Guerin is a loss of secreted lytic function required for invasion of lung interstitial tissue. Proc Natl Acad Sci USA, 100(21): 12420–12425PubMedCentralPubMedGoogle Scholar
  59. Hudelson P (1996). Gender differentials in tuberculosis: the role of socio-economic and cultural factors. Tuber Lung Dis, 77(5): 391–400PubMedGoogle Scholar
  60. Jones B E, Young SM, Antoniskis D, Davidson P T, Kramer F, Barnes P F (1993). Relationship of the manifestations of tuberculosis to CD4 cell counts in patients with human immunodeficiency virus infection. Am Rev Respir Dis, 148(5): 1292–1297PubMedGoogle Scholar
  61. Jouanguy E, Altare F, Lamhamedi S, Revy P, Emile J F, Newport M, Levin M, Blanche S, Seboun E, Fischer A, Casanova J L (1996). Interferon-gamma-receptor deficiency in an infant with fatal bacille Calmette-Guérin infection. N Engl J Med, 335(26): 1956–1961PubMedGoogle Scholar
  62. Kapur V, Whittam T S, Musser J M (1994). Is Mycobacterium tuberculosis 15, 000 years old? J Infect Dis, 170(5): 1348–1349PubMedGoogle Scholar
  63. Kaufmann S H (2002). Protection against tuberculosis: cytokines, T cells, and macrophages. Ann Rheum Dis, 61(Suppl 2): ii54–ii58PubMedCentralPubMedGoogle Scholar
  64. Keane J, Gershon S, Wise R P, Mirabile-Levens E, Kasznica J, Schwieterman W D, Siegel J N, Braun M M (2001). Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med, 345(15): 1098–1104PubMedGoogle Scholar
  65. Kim J H, Lee S Y, Lee S H, Sin C, Shim J J, In K H, Yoo S H, Kang K H (2003). NRAMP1 genetic polymorphisms as a risk factor of tuberculous pleurisy. Int J Tuberc Lung Dis, 7(4): 370–375PubMedGoogle Scholar
  66. Kinhikar A G, Verma I, Chandra D, Singh K K, Weldingh K, Andersen P, Hsu T, Jacobs W R Jr, Laal S (2010). Potential role for ESAT6 in dissemination of M. tuberculosis via human lung epithelial cells. Mol Microbiol, 75(1): 92–106PubMedCentralPubMedGoogle Scholar
  67. Kumar A, Bose M, Brahmachari V (2003). Analysis of expression profile of mammalian cell entry (mce) operons of Mycobacterium tuberculosis. Infect Immun, 71(10): 6083–6087PubMedCentralPubMedGoogle Scholar
  68. Lado Lado F L, Barrio Gómez E, Carballo Arceo E, Cabarcos Ortíz de Barrón A, Lado F L, Barrio Gómez E (1999). Clinical presentation of tuberculosis and the degree of immunodeficiency in patients with HIV infection. Scand J Infect Dis, 31(4): 387–391PubMedGoogle Scholar
  69. Lebrun P, Raze D, Fritzinger B, Wieruszeski J M, Biet F, Dose A, Carpentier M, Schwarzer D, Allain F, Lippens G, Locht C (2012). Differential contribution of the repeats to heparin binding of HBHA, a major adhesin of Mycobacterium tuberculosis. PLoS ONE, 7(3): e32421PubMedCentralPubMedGoogle Scholar
  70. Lee M P, Chan J W, Ng K K, Li P C (2000). Clinical manifestations of tuberculosis in HIV-infected patients. Respirology, 5(4): 423–426PubMedGoogle Scholar
  71. Levin M, Newport M J, D’Souza S, Kalabalikis P, Brown I N, Lenicker H M, Agius P V, Davies E G, Thrasher A, Klein N, et al (1995). Familial disseminated atypical mycobacterial infection in childhood: a human mycobacterial susceptibility gene?. Lancet, 345(8942): 79–83PubMedGoogle Scholar
  72. Lin C Y, Chen T C, Lu P L, Lai C C, Yang Y H, Lin W R, Huang P M, Chen Y H (2013). Effects of gender and age on development of concurrent extrapulmonary tuberculosis in patients with pulmonary tuberculosis: a population based study. PLoS ONE, 8(5): e63936PubMedCentralPubMedGoogle Scholar
  73. Lin P L, Myers A, Smith L, Bigbee C, Bigbee M, Fuhrman C, Grieser H, Chiosea I, Voitenek N N, Capuano S V, Klein E, Flynn J L (2010). Tumor necrosis factor neutralization results in disseminated disease in acute and latent Mycobacterium tuberculosis infection with normal granuloma structure in a cynomolgus macaque model. Arthritis Rheum, 62(2): 340–350PubMedCentralPubMedGoogle Scholar
  74. Liu P T, Stenger S, Li H, Wenzel L, Tan B H, Krutzik S R, Ochoa M T, Schauber J, Wu K, Meinken C, Kamen D L, Wagner M, Bals R, Steinmeyer A, Zügel U, Gallo R L, Eisenberg D, Hewison M, Hollis B W, Adams J S, Bloom B R, Modlin R L (2006). Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science, 311(5768): 1770–1773PubMedGoogle Scholar
  75. MacMicking J D, Taylor G A, McKinney J D (2003). Immune control of tuberculosis by IFN-gamma-inducible LRG-47. Science, 302(5645): 654–659PubMedGoogle Scholar
  76. Malik Z A, Iyer S S, Kusner D J (2001). Mycobacterium tuberculosis phagosomes exhibit altered calmodulin-dependent signal transduction: contribution to inhibition of phagosome-lysosome fusion and intracellular survival in human macrophages. J Immunol, 166(5): 3392–3401PubMedGoogle Scholar
  77. Manca C, Tsenova L, Bergtold A, Freeman S, Tovey M, Musser J M, Barry C E 3rd, Freedman V H, Kaplan G (2001). Virulence of a Mycobacterium tuberculosis clinical isolate in mice is determined by failure to induce Th1 type immunity and is associated with induction of IFN-alpha /beta. Proc Natl Acad Sci USA, 98(10): 5752–5757PubMedCentralPubMedGoogle Scholar
  78. Martineau A R, Wilkinson R J, Wilkinson K A, Newton S M, Kampmann B, Hall B M, Packe G E, Davidson R N, Eldridge S M, Maunsell Z J, Rainbow S J, Berry J L, Griffiths C J (2007). A single dose of vitamin D enhances immunity to mycobacteria. Am J Respir Crit Care Med, 176(2): 208–213PubMedGoogle Scholar
  79. Martinez A N, Rhee J T, Small PM, Behr MA (2000). Sex differences in the epidemiology of tuberculosis in San Francisco. Int J Tuberc Lung Dis, 4(1): 26–31PubMedGoogle Scholar
  80. McDonough K A, Kress Y (1995). Cytotoxicity for lung epithelial cells is a virulence-associated phenotype of Mycobacterium tuberculosis. Infect Immun, 63(12): 4802–4811PubMedCentralPubMedGoogle Scholar
  81. McDonough K A, Kress Y, Bloom B R (1993). Pathogenesis of tuberculosis: interaction of Mycobacterium tuberculosis with macrophages. Infect Immun, 61(7): 2763–2773PubMedCentralPubMedGoogle Scholar
  82. McKinney J D, Höner zu Bentrup K, Muñoz-Elías E J, Miczak A, Chen B, Chan W T, Swenson D, Sacchettini J C, Jacobs W R Jr, Russell D G (2000). Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase. Nature, 406(6797): 735–738PubMedGoogle Scholar
  83. Menozzi F D, Bischoff R, Fort E, Brennan M J, Locht C (1998). Molecular characterization of the mycobacterial heparin-binding hemagglutinin, a mycobacterial adhesin. Proc Natl Acad Sci USA, 95(21): 12625–12630PubMedCentralPubMedGoogle Scholar
  84. Menozzi F D, Rouse J H, Alavi M, Laude-Sharp M, Muller J, Bischoff R, Brennan M J, Locht C (1996). Identification of a heparin-binding hemagglutinin present in mycobacteria. J Exp Med, 184(3): 993–1001PubMedGoogle Scholar
  85. Musellim B, Erturan S, Sonmez Duman E, Ongen G (2005). Comparison of extra-pulmonary and pulmonary tuberculosis cases: factors influencing the site of reactivation. Int J Tuberc Lung Dis, 9(11): 1220–1223PubMedGoogle Scholar
  86. Nathan C, Shiloh M U (2000). Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens. Proc Natl Acad Sci USA, 97(16): 8841–8848PubMedCentralPubMedGoogle Scholar
  87. Nursyam E W, Amin Z, Rumende C M (2006). The effect of vitamin D as supplementary treatment in patients with moderately advanced pulmonary tuberculous lesion. Acta Med Indones, 38(1): 3–5PubMedGoogle Scholar
  88. Peters W, Ernst J D (2003). Mechanisms of cell recruitment in the immune response to Mycobacterium tuberculosis. Microbes Infect, 5(2): 151–158PubMedGoogle Scholar
  89. Pethe K, Alonso S, Biet F, Delogu G, Brennan M J, Locht C, Menozzi F D (2001). The heparin-binding haemagglutinin of M. tuberculosis is required for extrapulmonary dissemination. Nature, 412(6843): 190–194PubMedGoogle Scholar
  90. Pitchenik A E, Fertel D, Bloch A B (1988). Mycobacterial disease: epidemiology, diagnosis, treatment, and prevention. Clin Chest Med, 9(3): 425–441PubMedGoogle Scholar
  91. Raviglione M C, Narain J P, Kochi A (1992). HIV-associated tuberculosis in developing countries: clinical features, diagnosis, and treatment. Bull World Health Organ, 70(4): 515–526PubMedCentralPubMedGoogle Scholar
  92. Reed M B, Domenech P, Manca C, Su H, Barczak A K, Kreiswirth B N, Kaplan G, Barry C E 3rd (2004). A glycolipid of hypervirulent tuberculosis strains that inhibits the innate immune response. Nature, 431(7004): 84–87PubMedGoogle Scholar
  93. Rengarajan J, Bloom B R, Rubin E J (2005). Genome-wide requirements for Mycobacterium tuberculosis adaptation and survival in macrophages. Proc Natl Acad Sci USA, 102(23): 8327–8332PubMedCentralPubMedGoogle Scholar
  94. Rieder H L, Snider D E Jr, Cauthen G M (1990). Extrapulmonary tuberculosis in the United States. Am Rev Respir Dis, 141(2): 347–351PubMedGoogle Scholar
  95. Rook G A, Hernandez-Pando R (1996). The pathogenesis of tuberculosis. Annu Rev Microbiol, 50(1): 259–284PubMedGoogle Scholar
  96. Sassetti C M, Rubin E J (2003). Genetic requirements for mycobacterial survival during infection. Proc Natl Acad Sci USA, 100(22): 12989–12994PubMedCentralPubMedGoogle Scholar
  97. Schnappinger D, Ehrt S, Voskuil MI, Liu Y, Mangan J A, Monahan IM, Dolganov G, Efron B, Butcher P D, Nathan C, Schoolnik G K (2003). Transcriptional adaptation of Mycobacterium tuberculosis within Macrophages: Insights into the phagosomal environment. J Exp Med, 198(5): 693–704PubMedCentralPubMedGoogle Scholar
  98. Shafer R W, Kim D S, Weiss J P, Quale J M (1991). Extrapulmonary tuberculosis in patients with human immunodeficiency virus infection. Medicine (Baltimore), 70(6): 384–397Google Scholar
  99. Shiloh M U, Nathan C F (2000). Reactive nitrogen intermediates and the pathogenesis of Salmonella and Mycobacteria. Curr Opin Microbiol, 3(1): 35–42PubMedGoogle Scholar
  100. Sita-Lumsden A, Lapthorn G, Swaminathan R, Milburn H J (2007). Reactivation of tuberculosis and vitamin D deficiency: the contribution of diet and exposure to sunlight. Thorax, 62(11): 1003–1007PubMedCentralPubMedGoogle Scholar
  101. Sly L M, Hingley-Wilson S M, Reiner N E, McMaster W R (2003). Survival of Mycobacterium tuberculosis in host macrophages involves resistance to apoptosis dependent upon induction of antiapoptotic Bcl-2 family member Mcl-1. J Immunol, 170(1): 430–437PubMedGoogle Scholar
  102. Snider D E Jr, Roper W L (1992). The new tuberculosis. N Engl J Med, 326(10): 703–705PubMedGoogle Scholar
  103. Sohn H, Kim J S, Shin S J, Kim K, Won C J, Kim WS, Min K N, Choi H G, Lee J C, Park J K, Kim H J (2011). Targeting of Mycobacterium tuberculosis heparin-binding hemagglutinin to mitochondria in macrophages. PLoS Pathog, 7(12): e1002435PubMedCentralPubMedGoogle Scholar
  104. Sreeramareddy C T, Panduru K V, Verma S C, Joshi H S, Bates M N (2008). Comparison of pulmonary and extrapulmonary tuberculosis in Nepal- a hospital-based retrospective study. BMC Infect Dis, 8(1): 8PubMedCentralPubMedGoogle Scholar
  105. Sudre P, ten Dam G, Kochi A (1992). Tuberculosis: a global overview of the situation today. Bull World Health Organ, 70(2): 149–159PubMedCentralPubMedGoogle Scholar
  106. Tascon R E, Soares C S, Ragno S, Stavropoulos E, Hirst EM, Colston M J (2000). Mycobacterium tuberculosis-activated dendritic cells induce protective immunity in mice. Immunology, 99(3): 473–480PubMedCentralPubMedGoogle Scholar
  107. Theuer C P, Hopewell P C, Elias D, Schecter G F, Rutherford G W, Chaisson R E (1990). Human immunodeficiency virus infection in tuberculosis patients. J Infect Dis, 162(1): 8–12PubMedGoogle Scholar
  108. Thuong N T, Hawn T R, Thwaites G E, Chau T T, Lan N T, Quy H T, Hieu N T, Aderem A, Hien T T, Farrar J J, Dunstan S J (2007). A polymorphism in human TLR2 is associated with increased susceptibility to tuberculous meningitis. Genes Immun, 8(5): 422–428PubMedGoogle Scholar
  109. Tsenova L, Ellison E, Harbacheuski R, Moreira A L, Kurepina N, Reed M B, Mathema B, Barry C E 3rd, Kaplan G (2005). Virulence of selected Mycobacterium tuberculosis clinical isolates in the rabbit model of meningitis is dependent on phenolic glycolipid produced by the bacilli. J Infect Dis, 192(1): 98–106PubMedGoogle Scholar
  110. van Pinxteren L A, Cassidy J P, Smedegaard B H, Agger E M, Andersen P (2000). Control of latent Mycobacterium tuberculosis infection is dependent on CD8 T cells. Eur J Immunol, 30(12): 3689–3698PubMedGoogle Scholar
  111. Verway M, Bouttier M, Wang T T, Carrier M, Calderon M, An B S, Devemy E, McIntosh F, Divangahi M, Behr M A, White J H (2013). Vitamin D induces interleukin-1β expression: paracrine macrophage epithelial signaling controls M. tuberculosis infection. PLoS Pathog, 9(6): e1003407PubMedCentralPubMedGoogle Scholar
  112. Wang T T, Nestel F P, Bourdeau V, Nagai Y, Wang Q, Liao J, Tavera-Mendoza L, Lin R, Hanrahan J W, Mader S, White J H (2004). Cutting edge: 1, 25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol, 173(5): 2909–2912PubMedGoogle Scholar
  113. Weir M R, Thornton G F (1985). Extrapulmonary tuberculosis. Experience of a community hospital and review of the literature. Am J Med, 79(4): 467–478PubMedGoogle Scholar
  114. WHO (2014). Global tuberculosis control 2013.Google Scholar
  115. Wilkinson R J, Llewelyn M, Toossi Z, Patel P, Pasvol G, Lalvani A, Wright D, Latif M, Davidson R N (2000). Influence of vitamin D deficiency and vitamin D receptor polymorphisms on tuberculosis among Gujarati Asians in west London: a case-control study. Lancet, 355(9204): 618–621PubMedGoogle Scholar
  116. Wilkinson R J, Patel P, Llewelyn M, Hirsch C S, Pasvol G, Snounou G, Davidson R N, Toossi Z (1999). Influence of polymorphism in the genes for the interleukin (IL)-1 receptor antagonist and IL-1beta on tuberculosis. J Exp Med, 189(12): 1863–1874PubMedCentralPubMedGoogle Scholar
  117. Wolf A J, Linas B, Trevejo-Nuñez G J, Kincaid E, Tamura T, Takatsu K, Ernst J D (2007). Mycobacterium tuberculosis infects dendritic cells with high frequency and impairs their function in vivo. J Immunol, 179(4): 2509–2519PubMedGoogle Scholar
  118. Yang Z, Kong Y, Wilson F, Foxman B, Fowler A H, Marrs C F, Cave M D, Bates J H (2004). Identification of risk factors for extrapulmonary tuberculosis. Clin Infect Dis, 38(2): 199–205PubMedGoogle Scholar
  119. Zhang X, Andersen A B, Lillebaek T, Kamper-Jørgensen Z, Thomsen V O, Ladefoged K, Marrs C F, Zhang L, Yang Z (2011). Effect of sex, age, and race on the clinical presentation of tuberculosis: a 15-year population-based study. Am J Trop Med Hyg, 85(2): 285–290PubMedCentralPubMedGoogle Scholar

Copyright information

© Higher Education Press and Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.The Department of Microbiology, Immunology and BiochemistryUniversity of Tennessee Health Science CenterMemphisUSA

Personalised recommendations