Immunomodulatory Role of Bacillus Calmette-Guérin in the Prevention and Therapy of Allergy and Asthma

  • Toluwalope O. Makinde
  • Againdra K. Bewtra
  • Devendra K. Agrawal
Part of the Allergy Frontiers book series (ALLERGY, volume 5)

There has been an increased prevalence and severity of asthma in recent decades. This increase in episodes of allergic asthma has been more evident in westernized nations where most infectious diseases have been markedly reduced by early immunization programs and extensive use of antibiotics [1]. Better diagnosis and exposure to conventional allergens have not been able to sufficiently explain the increased incidence of asthma. A substantial shift in genome does not occur in the span of only a few decades, and so genetic predisposition has also been ruled out as a major factor contributing to the observed increase in atopic diseases [1]. Paradoxically, several investigators have observed an inverse relationship between atopic diseases, such as asthma, and exposure to infectious pathogens including Mycobacterium bacilli [2].

Many immune cells and mediators contribute to the development and exacerbation of allergic response and asthma. It is, therefore, not surprising to see the development of numerous drugs to combat the disease. None of these therapies has a curative effect and there still remains a cohort of patients who are unresponsive to these treatments [3]. This warrants continued research in this area to develop more effective therapeutic approaches with minimal side effects to control this debilitating disease. In the following sections, we critically reviewed the role of BCG in preventing a T helper (TH) 2 response, its effect on immune cells, and its efficacy as a potential therapeutic agent to control allergy and asthma.


Tuberculin Skin Test Allergic Asthma Atopic Disease Mycobacterium Bovis Mycobacterial Antigen 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Cookson WO, Moffatt MF (1997) Asthma: an epidemic in the absence of infection? Science 275:41–42CrossRefPubMedGoogle Scholar
  2. 2.
    Barlan IB, Bahceciler N, Akdis M, Akdis CA (2005) Role of bacillus Calmette-Guerin as an immunomodulator for the prevention and treatment of allergy and asthma. Current Opinion in Allergic and Clinical Immunology 5:552–557CrossRefGoogle Scholar
  3. 3.
    Silverman R (2000) Treatment of acute asthma. A new look at the old and the new. Clinics in Chest Medicine 21:361–379CrossRefPubMedGoogle Scholar
  4. 4.
    Strachan DP (2000) Family size, infection and atopy: the first decade of the “hygiene hypothesis”. Thorax 1:S2–10CrossRefGoogle Scholar
  5. 5.
    Eigen H (1999) The RSV-asthma link: the emerging story. Introduction. Journal of Pediatrics 135:1–5CrossRefPubMedGoogle Scholar
  6. 6.
    Roth A, Gustafson P, Nhaga A, Djana Q, Poulsen A, Garly ML, Jensen H, Sodeman M, Rodrigues A, Aaby P (2005) BCG vaccination scar associated with better childhood survival in Guinea-Bissau. International Journal of Epidemiology 34:540–547CrossRefPubMedGoogle Scholar
  7. 7.
    Alexandroff AB, Jackson AM, O'Donnell MA, James K (1999) BCG immunotherapy of bladder cancer: 20 years on. Lancet 353:1689–1694CrossRefPubMedGoogle Scholar
  8. 8.
    Aguirre-Blanco AM, Lukey PT, Cliff JM, Dockrell HM (2007) Strain dependent variation in Mycobacteria bovis BCG-induced human T-cell activation and gamma interferon production in vitro. Infection and Immunity 75:3197–3201CrossRefPubMedGoogle Scholar
  9. 9.
    Aldovini A, Young RA (1991) Humoral and cell-mediated immune response to live recombinant BCG-HIV vaccine. Nature 351(6326):479–482CrossRefPubMedGoogle Scholar
  10. 10.
    Aaby P, Shaheen SO, Heyes CB, Goudiaby A, Hall AJ, Shiell AW, Jensen H, Marchant A (2000) Early BCG vaccination and reduction in atopy in Guinea-Bissau. Clinical Experimental Allergy 30:644–650CrossRefGoogle Scholar
  11. 11.
    Grüber C, Kulig M, Bergmann R, Guggenmoos-Holzmann I, Wahn U; MAS-90 study group(2001) Delayed hypersensitivity to tuberculin, total immunoglobulin E, specific sensiti-zation, and atopic manifestation in longitudinally followed early bacilli Calmette-Guérin-vaccinated and non-vaccinated children. Pediatrics 107:E36CrossRefPubMedGoogle Scholar
  12. 12.
    Bager P, Rostgaard K, Nielsen NM, Melbye M, Westergaard T (2003) Age of bacilli Calmette-Guerin vaccination and risk of allergy and asthma. Clinical and Experimental Allergy 33:1512–1517CrossRefPubMedGoogle Scholar
  13. 13.
    Townley RG, Barlan IB, Patino C, Vichyanond P, Minervini MC, Simasathien T, Nettagul R, Bahceciler NN, Basdemir D, Akkoc T, Pongprueksa S, Hopp RJ (2004) The effect of BCG vaccine at birth on the development of atopy or allergic disease in young children. Annals of Allergy, Asthma and Immunology 92:350–355CrossRefGoogle Scholar
  14. 14.
    Marks GB, Ng K, Zhou J, Toelle BG, Xuan W, Belousova EG, Britton WJ (2003) The effect of neonatal BCG vaccination on atopy and asthma at age 7 to 14 years: a historical cohort study in a community with a very low prevalence of tuberculosis infection and a high prevalence of atopic disease. The Journal of Allergy Clinical Immunology 111:541–549CrossRefGoogle Scholar
  15. 15.
    Hopfenspirger MT, Parr SK, Hopp RJ, Townley RG, Agrawal DK (2001) Mycobacterial antigens attenuate late phase response, airway hyperresponsiveness, and brochoalveolar lavage eosinophilia in a mouse model of bronchial asthma. International Immunopharmacology 1:1743–1751CrossRefPubMedGoogle Scholar
  16. 16.
    Wang S, Fan Y, Han X, Yang J, Bilenki L, Yang X (2001) IL-12-dependent vascular cell adhesion molecule-1 expression contributes to airway eosinophilic inflammation in a mouse model of asthma-like reaction. The Journal of Immunology 166:2741–2749PubMedGoogle Scholar
  17. 17.
    Hopfenspirger MT, Agrawal DK (2002) Airway hyperresponsiveness, late allergic response, and eosinophilia are reversed with mycobacterial antigens in ovalbumin-presensitized mice. The Journal of Immunology 168:2516–2522PubMedGoogle Scholar
  18. 18.
    Yang X, Wang S, Fan Y, Zhu L (1999) Systemic mycobacterial infection inhibits antigen-specific immunoglobulin E production, bronchial mucus production and eosinophilic inflammation induced by allergen. Immunology 98:329–337CrossRefPubMedGoogle Scholar
  19. 19.
    Erb KJ, Holloway JW, Sobeck A, Moll H, Le Gros G (1998) Infection of mice with Mycobacterium bovis bacillus Calmette-Guerin (BCG) suppresses allergen-induced airway eosinophilia. The Journal of Experimental Medicine 187:561–569CrossRefPubMedGoogle Scholar
  20. 20.
    Hoft DF, Brown RM, Roodman ST. (1998) Bacilli Calmette-Guérin vaccination enhances human gamma delta T cell responsiveness to mycobacteria suggestive of a memory-like phe-notype. The Journal of Immunology 161:1045–1054PubMedGoogle Scholar
  21. 21.
    Hylkema MN, Timens W, Luinge M, Vander Der Werf N, Hoekstra MO (2002) The effect of bacillus Calmette-Guerin immunization depends on the genetic predisposition to Th2-type responsiveness. American Journal of Respiratory Cell and Molecular Biology 27:244–249PubMedGoogle Scholar
  22. 22.
    Shibata Y, Henriksen RA, Honda I, Nakamura RM, Myrvik ON (2005) Splenic PGE2-releasing macrophage regulate Th1 and Th2 immune responses in mice treated with heat-killed BCG. Journal of Leukocyte Biology 78:1281–1290CrossRefPubMedGoogle Scholar
  23. 23.
    Choi IS, Lin XH, Koh YA, Cui Y (2007) Inoculation route-dependent and allergen-specific suppressive effects of bacille Calmette-Guerin vaccination on asthmatic reactions in BALB/c mice. Lung 185:179–186CrossRefPubMedGoogle Scholar
  24. 24.
    Zhang GS, Shen HH (2005) [The preventive effect of bacillus Calmette-Guerin vaccination in early life on airway inflammation and mucus production in murine model of asthma]. Zhonghua Jie He He Hu Xi Za Zhi 28:17–21PubMedGoogle Scholar
  25. 25.
    Hopfenspirger MT (2003) Mycobacterial antigens and immunomodulation in allergic asthma. Ph.D. (Biomedical Sciences) Dissertation, Creighton University, Omaha, Nebraska, USAGoogle Scholar
  26. 26.
    Lai Y, Mohammed KA, Nasreen N, Baumuratov AS, Bellew BF, Antony VB (2007) Induction of cell cycle arrest and apoptosis by BCG infection in cultured human bronchial airway epithelial cells. American Journal of Physiology Lung - Cellular and Molecular Physiology 293: L393–401CrossRefPubMedGoogle Scholar
  27. 27.
    Mendez-Samperio P, Alba L, Trejo A. (2007) Mycobacterium bovis -mediated induction of human β -defensin-2 in epithelial cells is controlled by intracellular calcium and p38 MAPK. Journal of Infection 54:469–474CrossRefPubMedGoogle Scholar
  28. 28.
    Romagnani S (1992) Induction of TH1 and TH2 responses: a key role for the ‘natural’ immune response? Immunology Today 13:379–381CrossRefPubMedGoogle Scholar
  29. 29.
    Shirakawa T, Enomoto T, Shimazu S, Hopkin JM (1997) The inverse association between tuberculin responses and atopic disorder. Science 275:77–79CrossRefPubMedGoogle Scholar
  30. 30.
    Marchant A, Goetghebuer T, Ota MO, Wolfe I, Ceesay SJ, De Groote D, Corrah T, Bennett S, Wheeler J, Huygen K, Aaby P, McAdam KP, Newport MJ (1999) Newborns develop a Th1-type immune response to Mycobacterium bovis bacillus Calmette-Guerin vaccination. The Journal of Immunology 163:2249–2255PubMedGoogle Scholar
  31. 31.
    Cho SH, Stanciu LA, Holgate ST, Johnston SL (2005) Increased interleukin-4, interleukin-5, and interferon-gamma in airway CD4 + and CD8 + T cells in atopic asthma. American Journal of Respiratory and Critical Care Medicine 171:224–230CrossRefPubMedGoogle Scholar
  32. 32.
    Kim YK, Oh SY, Jeon SG, Park HW, Lee SY, Chun EY, Bang B, Lee HS, Oh MH, Kim YS, Kim JH, Gho YS, Cho SH, Min KU, Kim YY, Zhu Z (2007) Airway exposure levels of lipopolysaccharide determine type 1 versus type 2 experimental asthma. The Journal of Immunology 178:5375–5382PubMedGoogle Scholar
  33. 33.
    Asosingh K, Swaidani S, Aronica M, Erzurum SC (2007) Th1- and Th2-dependent endothe-lial progenitor cell recruitment and angiogenic switch in asthma. The Journal of Immunology 178:6482–6494PubMedGoogle Scholar
  34. 34.
    Nahori MA, Lagranderie M, Lefort J, Thouron F, Joseph D, Winter N, Gicquel B, Lapa e Silva JR, Vargaftig BB (2001) Effect of Mycobacterium bovis BCG on the development of allergic inflammation and bronchial hyperresponsiveness in hyper-IgE BP2 mice vaccinated as newborn. Vaccine 19:1484–1495CrossRefPubMedGoogle Scholar
  35. 35.
    Xu G, Li Y, Yang J, Zhou X, Yin X, Liu M, Zhao D (2007) Effect of recombinant Mce4A protein of Mycobacterium bovis on expression of TNF-alpha, iNOS, IL-6, and IL12 in bovine alveolar macrophages. Molecular and Cellular Biochemistry 302:1–7CrossRefPubMedGoogle Scholar
  36. 36.
    Zuany-Amorim C, Manlius C, Trifilieff A, Brunet LR, Rook G, Bowen G, Pay G, Walker C (2002) Long term protective and antigen-specific effect of heat-killed Mycobacterium vaccae in a murine model of allergy pulmonary inflammation. The Journal of Immunology 169:1492–1499PubMedGoogle Scholar
  37. 37.
    Xia Y, Zhang JH, Ji ZH, Li XD, Yu ZW, Liu HY (2006) [Effect of bacillus Calmette-Guerin treatment on airway inflammation and T regulatory cells in mice with asthma]. Zhongguo Dang Dai Er Ke Za Zhi 8:413–416PubMedGoogle Scholar
  38. 38.
    Su Yc, Peng HJ, Wang SR, Han SH, Tsai JJ (2001) Effect of BCG on ovalbumin-induced bronchial hyperreactivity in a guinea pig model. The Journal of Microbiology, Immunology and Infections 34:25–34Google Scholar
  39. 39.
    Jason J, Archibald LK, Nwanyanwu OC, Kazembe PN, Chatt JA, Norton E, Dobbie H, Jarvis WR (2002) Clinical and immune impact of Mycobacterium bovis BCG vaccination scarring. Infection and Immunity 70:6188–6195CrossRefPubMedGoogle Scholar
  40. 40.
    Xia Y, Zhang Jh, Ji ZH, Li XD, Yu ZW, Liu HY (2006) [Effect of bacillus Calmette-Guerin treatment on airway inflammation and T regulatory cells in mice with asthma]. Zhonqquo Dan Dai Er Ke Za Zhi 8:413–416Google Scholar
  41. 41.
    McGee HS, Agrawal DK (2009) Naturally occurring and inducible T regulatory cells modulating immune response in allergic asthma. American Journal of Respiratory and Critical Care Medicine 180:211–225CrossRefPubMedGoogle Scholar
  42. 42.
    Koh YI, Choi IS, Lee JJ (2004) Effects of cytokine milieu secreted by BCG-treated dendritic cells on allergen-specific Th immune response. Journal of Korean Medical Science 19:640–646PubMedGoogle Scholar
  43. 43.
    Madura Larsen J, Stabell Benn C, Fillie Y, Van der Kleij D, Aaby P, Yazdanbakhsh M (2007) BCG stimulated dendritic cells induce an interleukin-10 producing T-cell population with no T helper 1 or T helper 2 bias in vitro. Immunology 121:276–282CrossRefPubMedGoogle Scholar
  44. 44.
    McGee HS, Agrawal DK (2006) Th2 cells in the pathogenesis of airway remodeling: regulatory T cells a plausible panacea for asthma. Immunologic Research 35:219–232CrossRefPubMedGoogle Scholar
  45. 45.
    Makinde T, Murphy RF, Agrawal DK (2007) The regulatory role of TGF-β in airway remodeling in asthma. Immunology and Cell Biology 85:348–356CrossRefPubMedGoogle Scholar
  46. 46.
    Smith SM, Malin AS, Pauline T, Lukey, Atkinson SE, Content J, Huygen K, Dockrell HM (1999) Characterization of human Mycobacterium bovis bacille Calmette-Guerin-reactive CD8+ T cells. Infection and Immunity 67:5223–5230PubMedGoogle Scholar
  47. 47.
    Serbina NV, Liu CC, Scanga CA, Flynn JL (2000) CD8+ CTL from lungs of Mycobacterium tuberculosis -infected mice express perforin in vivo and lyse infected macrophages. The Journal of Immunology 165:353–363PubMedGoogle Scholar
  48. 48.
    Tascon RE, Stavropoulos E, Lukacs KV, Colston MJ (1998) Protection against Mycobacterium tuberculosis infection by CD8+ T cells requires the production of gamma interferon. Infection and Immunity 66:830–834PubMedGoogle Scholar
  49. 49.
    Ngai P, McCormick S, Small C, Zhang X, Zganiacz A, Aoki N, Xing Z (2007) Gamma interferon responses of CD4 and CD8 T-cell subsets are quantitatively different and independent of each other during pulmonary Mycobacterium bovis BCG infection. Infection and Immunity 75:2244–2252CrossRefPubMedGoogle Scholar
  50. 50.
    Wang J, Santosuosso M, Ngai P, Zganiacz A, Xing Z (2004) Activation of CD8 T cells by mycobacterial vaccination protects against pulmonary tuberculosis in the absence of CD4 T cells. The Journal of Immunology 173:4590–4597PubMedGoogle Scholar
  51. 51.
    Ladel CH, Daugelat S, Kaufmann SH (1995) Immune response to Mycobacterium bovis bacille Calmette Guerin infection in major histocompatibility complex class I- and II-deficient knock-out mice: contribution of CD4 and CD8 T cells to acquired resistance. European Journal of Immunology 25:377–384CrossRefPubMedGoogle Scholar
  52. 52.
    Murray RA, Mansoor N, Harbacheuski R, Soler J, Davids V, Soares A, Hawkridge A, Hussey GD, Maeker H, Kaplan G, Hanekom WA (2006) Bacillus Calmette Guerin vaccination of human newborns induces a specific, functional CD8+ T cell response. The Journal of Immunology 177:5647–5651PubMedGoogle Scholar
  53. 53.
    Hope JC, Kwong LS, Sopp P, Collins RA, Howard CJ (2000) Dendritic cells induce CD4+ and CD8+ T-cell responses to Mycobacterium bovis and M. avium antigens in bacille Calmette Guerin vaccinated and nonvaccinated cattle. Scandinavian Journal Immunology 52:285–291CrossRefGoogle Scholar
  54. 54.
    Abate G, Eslick J, Newman FK, Frey SE, Belshe RB, Monath TP, Hoft DF (2005) Flow-cytometric detection of vaccinia-induced memory effector CD4(+), CD8(+), and gamma delta TCR(+) T cells capable of antigen-specific expansion and effector functions. The Journal of Infectious Diseases 192:1362–1371CrossRefPubMedGoogle Scholar
  55. 55.
    Vila LM, Haftel HM, Park HS, Lin MS, Romzek NC, Hanash SM, Holoshitz J (1995) Expansion of Mycobacterium -reactive gamma delta T cells by a subset of memory helper T cells. Infection and Immunity 63:1211–1217PubMedGoogle Scholar
  56. 56.
    Born W, Cady C, Jones-Carson J, Mukasa A, Lahn M, O'Brien R (1999). Immunoregulatory functions of gamma delta T cells. Advances in Immunology 71:77–144CrossRefPubMedGoogle Scholar
  57. 57.
    Ravn P, Boesen H, Pedersen BK, Andersen P (1997) Human T cell responses induced by vaccination with Mycobacterium bovis bacillus Calmette-Guerin. Journal of Immunology 158:1949–1955Google Scholar
  58. 58.
    Caccamo N, Sireci G, Meraviglia S, Dieli F, Ivanyi J, Salerno A (2006) gammadelta T cells condition dendritic cells in vivo for priming pulmonary CD8 T cell responses against Mycobacterium tuberculosis. European Journal of Immunology 36:2681–1690CrossRefPubMedGoogle Scholar
  59. 59.
    Boismenu R, Feng L, Xia YY, Chang JC, Havran WL (1996) Chemokine expression by intra-epithelial gamma delta T cells. Implications for the recruitment of inflammatory cells to damaged epithelia. The Journal of Immunology 157:985–992PubMedGoogle Scholar
  60. 60.
    Kabelitz D, Wesch D (2003) Features and functions of gamma delta T lymphocytes: focus on chemokines and their receptors. Critical Review in Immunology 23:339–370CrossRefGoogle Scholar
  61. 61.
    Pechhold K, Wesch D, Schondelmaier S, Kabelitz D (1994) Primary activation of Vgamma 9-expressing gamma delta T cells by Mycobacterium tuberculosis. Requirement for Th1-type CD4 T cell help and inhibition by IL-10. The Journal of Immunology 152:4984–4992PubMedGoogle Scholar
  62. 62.
    Harada M, Magara-Koyanagi K, Watarai H, Nagata Y, Ishii Y, Kojo S, Horiguchi S, Okamoto Y, Nakayama T, Suzuki N, Yeh WC, Akira S, Kitamura H, Ohara O, Seino K, Taniguchi M (2006) IL-12-induced Bepsilon cell apoptosis mediated by natural killer T cells suppresses IgE responses. The Journal of Experimental Medicine 203:2929–2937CrossRefPubMedGoogle Scholar
  63. 63.
    Emoto M, Emoto Y, Buchwalow IB, Kaufmann SH (1999) Induction of IFN-gamma-producing CD4 + natural killer T cells by Myobacterium bovis bacillus Calmette Guerin. European Journal of Immunology 29:650–659CrossRefPubMedGoogle Scholar
  64. 64.
    Dieli F, Taniguchi M, Kronenberg M, Sidobre S, Ivanyi J, Fattorini L, Iona E, Orefici G, De Leo G, Russo D, Caccamo N, Sireci G, Di Sano C, Salerno A (2003) An anti-inflammatory role for V alpha14 NK T cells in Mycobacterium bovis bacillus Calmette-Guérin-infected mice. The Journal of Immunology 171:1961–1968PubMedGoogle Scholar
  65. 65.
    Saxena RK, Weissman D, Saxena QB, Simpson J, Lewis DM (2002) Kinetics of changes in lymphocyte subpopulations in mouse lungs after intrapulmonary infection with M. bovis (bacillus Calmette-Guerin) and identity of cells responsible for IFNgamma responses. Clinical and Experimental Immunology 128:405–410CrossRefPubMedGoogle Scholar
  66. 66.
    Tang C, Inman MD, van Rooijen N, Yang P, Shen H, Matsumoto K, O'Byrne PM (2001). The type 1-stimulating activity of lung macrophages inhibits Th2-mediated allergic airway inflammation by an IFN-gamma-dependent mechanism. The Journal of Immunology 166:1471–1481PubMedGoogle Scholar
  67. 67.
    Henderson RA, Watkins SC, Flynn JL (1997) Activation of human dendritic cells following infection with Mycobacterium tuberculosis. The Journal of Immunology 159:635–643PubMedGoogle Scholar
  68. 68.
    Kim KD, Lee HG, Kim JK, Park SN, Choe IS, Choe YK, Kim SJ, Lee E, Lim JS (1999) Enhanced antigen-presenting activity and tumor necrosis factor-alpha-independent activation of dendritic cells following treatment with Mycobacterium bovis bacillus Calmette-Guerin. Immunology 97:626–633CrossRefPubMedGoogle Scholar
  69. 69.
    O'Donnell MA, Luo Y, Chen X, Szilvasi A, Hunter SE, Clinton SK (1999) Role of IL-12 in the induction and potentiation of IFN-gamma in response to bacillus Calmette-Guerin. Journal of Immunology 163:4246–4252Google Scholar
  70. 70.
    Romagnani S (2000) T-cell subsets (Th1 versus Th2). Annals of Allergy, Asthma and Immunology 85:9–18Google Scholar
  71. 71.
    Borish L, Aaron A, Rumbyrt J, Cvietusa P, Negri J, Wenzel S (1996) Interleukin-10 regulation in normal subjects and patients with asthma. Journal of Allergy and Clinical Immunology 97:1288–1296CrossRefPubMedGoogle Scholar
  72. 72.
    Alm JS, Sanjeevi CB, Miller EN, Dabadghao P, Lilja G, Pershagen G, Blackwell JM, Scheynius A (2002) Atopy in children in relation to BCG vaccination and genetic polymorphisms at SLC11A1 (formerly NRAMP1) and D2S1471. Gene Immunology 3:71–77CrossRefGoogle Scholar
  73. 73.
    Rook GA, Martinelli R, Brunet LR (2003) Innate immune response to mycobacteria and the downregulation of atopic responses. Current Opinion in Allergy and Clinical Immunology 3:337–342CrossRefPubMedGoogle Scholar
  74. 74.
    Smitt JJ, Van Loveren H, Hoekstra MO, Karimi K, Folkerts G, Nijkamp FP (2003) The Slc11a1 (Nramp1) gene controls efficacy of mycobacterial treatment of allergic asthma. The Journal of Immunology 171:754–760Google Scholar
  75. 75.
    Smitt JJ, Van Loveren H, Hoekstra MO, Nijkamp FP, Bloksma N (2003) Influence of the macrophage bacterial resistance gene Nramp1 (Sic11a1) on the induction of allergic asthma in mouse. FASEB Journal 17:958–960Google Scholar
  76. 76.
    Caramalho I, Lopes-Carvalho T, Ostler D, Zelenay S, Haury M, Demengeot J (2003) Regulatory T cells selectively express toll-like receptors and are activated by lipopolysaccha-ride. The Journal of Experimental Medicine 197:403–411CrossRefPubMedGoogle Scholar
  77. 77.
    Pandey S, Agrawal DK (2006) Immunobiology of toll-like receptors: emerging trends. Immunology and Cell Biology 84:333–341CrossRefPubMedGoogle Scholar
  78. 78.
    Lauener RP, Birchler T, Adamski J, Braun-Fahrlander C, Bufe A, Herz V, von Mutius E, Nowak D, Rieldler J, Waser M, Sennhauser FH; ALEX study group (2002) Expression of CD14 and Toll-like receptor 2 in farmers' and non-farmers' children. Lancet 360:465–466CrossRefPubMedGoogle Scholar
  79. 79.
    Oppmann B, Lesley R, Blom B, Timans JC, Xu Y, Hunte B, Vega F, Yu N, Wang J, Singh K, Zonin F, Vaisberg E, Churakova T, Liu M, Gorman D, Wagner J, Zurawski S, Liu Y, Abrams JS, Moore KW, Rennick D, de Waal-Malefyt R, Hannum C, Bazan JF, Kastelein RA (2000) Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 13:715–725CrossRefPubMedGoogle Scholar
  80. 80.
    Bochud PY, Hawn TR, Aderem A (2003) Cutting edge: a toll-like receptor 2 polymorphism that is associated with lepromatous leprosy is unable to mediate mycobacterial signaling. The Journal of Immunology 170:3451–3454PubMedGoogle Scholar
  81. 81.
    Iwasaki A, Medzhitov R (2004) Toll-like receptor control of adaptive immune responses. Nature Immunology 5:987–995CrossRefPubMedGoogle Scholar
  82. 82.
    Uehori J, Matsumoto M, Tsuji S, Akazawa T, Takeuchi O, Akira S, Kawata T, Azuma I, Toyoshima K, Seya T (2003) Simultaneous blocking of human toll-like receptors 2 and 4 suppresses myeloid dendritic cell activation induced by Mycobacterium bovis bacillus Calmette-Guerin peptidoglycan. Infection and Immunity 71:4238–4249CrossRefPubMedGoogle Scholar
  83. 83.
    Anis MM, Fulton SA, Reba SM, Harding CV, Boom WH (2007) Modulation of naïve CD4+ T-cell responses to an airway antigen during pulmonary mycobacterial infection. Infection and Immunity 75:2260–2268CrossRefPubMedGoogle Scholar
  84. 84.
    Eisenbarth SC, Piggott DA, Huleatt JW, Visintin I, Herrick CA, Bottomly K (2002) Lipopolysaccharide-enhanced, toll-like receptor 4 dependent T helper cell type 2 responses to inhaled antigen. The Journal of Experimental Medicine 196:1645–1651CrossRefPubMedGoogle Scholar
  85. 85.
    D'Avila H, Almeida PE, Roque NR, Castro-Faria-Neto HC, Bozza PT (2007) Toll-like receptor-2-mediated C-C chemokine receptor 3 and eotaxin-driven eosinophil influx induced by Mycobacterium bovis BCG pleurisy. Infection and Immunity 75:1507–1511CrossRefPubMedGoogle Scholar
  86. 86.
    Hao M, Bao L, Gao L, Zhang HD (2007) [Construction and screen of recombinant BCG strain expressing and secreting human interleukin 12 protein]. Sischuan Da Xue Xue Bao Yi Xue Ban 38:186–189Google Scholar
  87. 87.
    Luo Y, Yamada H, Chen X, Ryan AA, Evanoff DP, Triccas JA, O'Donnell MA (2004) Recombinant Mycobacterium bovis bacillus Calmette-Guérin (BCG) expressing mouse IL-18 augments Th1 immunity and macrophage cytotoxicity. Clinical and Experimental Immunology 137:24–34CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  • Toluwalope O. Makinde
    • 1
  • Againdra K. Bewtra
    • 2
  • Devendra K. Agrawal
    • 3
  1. 1.Department of Biomedical SciencesCreighton University School of MedicineOmahaUSA
  2. 2.Department of Internal MedicineCreighton University School of MedicineOmahaUSA
  3. 3.Departments of Biomedical SciencesInternal Medicine, and Medical Microbiology and Immunology, Creighton University School of MedicineOmahaUSA

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