J. Exp. Med., Volume 187, Number 4, February 16, 1998 561-569

Infection of Mice with Mycobacterium bovis-Bacillus Calmette-Guérin (BCG) Suppresses Allergen-induced Airway Eosinophilia

By Klaus Josef Erb,^* John W. Holloway,^* Alexandra Sobeck, Heidrun Moll, and Graham Le Gros^*

From ^* The Malaghan Institute of Medical Research, 7060 Wellington South, New Zealand; and the  Zentrum für Infektionsforschung der Universität Würzburg, D-97070 Würzburg, Germany

It has been proposed that the increase in prevalence and severity of atopic disorders inversely correlates with exposure to infectious diseases such as tuberculosis. We have investigated this issue by combining an intranasal Mycobacterium bovis-Bacillus Calmette-Guérin (BCG) infection with a murine model of allergen, (ovalbumin [OVA]) induced airway eosinophilia. BCG infection either 4 or 12 wk before allergen airway challenge resulted in a 90-95 and 60-70% reduction in eosinophilia within the lungs, respectively, compared to uninfected controls. The inhibition of airway eosinophilia correlated with a reduced level of IL-5 production by T cells from the lymph node draining the site of OVA challenge. Interestingly, BCG infection of the lung had no effect on IgG1 and IgE OVA-specific serum immunoglobulin or blood eosinophil levels. Furthermore, BCG-induced inhibition of airway eosinophilia was strongly reduced in interferon (IFN)- receptor-deficient mice and could be partially reversed by intranasal IL-5 application. Intranasal BCG infections could also reduce the degree of lung eosinophilia and IL-5 produced by T cells after Nippostrongylus brasiliensis infection. Taken together, our data suggest that IFN- produced during the T helper cell (Th)1 immune response against BCG suppresses the development of local inflammatory Th2 responses in the lung. Most importantly, this inhibition did not extend to the systemic immunoglobulin response against OVA. Our data support the view that mycobacterial infections have the potential to suppress the development of atopic disorders in humans.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Yokoi, T., Amakawa, R., Tanijiri, T., Sugimoto, H., Torii, Y., Amuro, H., Son, Y., Tajima, K., Liu, Y.-J., Ito, T., Fukuhara, S. (2008). Mycobacterium bovis Bacillus Calmette-Guerin suppresses inflammatory Th2 responses by inducing functional alteration of TSLP-activated dendritic cells. Int Immunol 20: 1321-1329 [Abstract] [Full Text]  
• Han, X., Fan, Y., Wang, S., Jiao, L., Qiu, H., Yang, X. (2008). NK Cells Contribute to Intracellular Bacterial Infection-Mediated Inhibition of Allergic Responses. J. Immunol. 180: 4621-4628 [Abstract] [Full Text]  
• Balicer, R. D., Grotto, I., Mimouni, M., Mimouni, D. (2007). Is Childhood Vaccination Associated With Asthma? A Meta-analysis of Observational Studies. Pediatrics 120: e1269-e1277 [Abstract] [Full Text]  
• Anis, M. M., Fulton, S. A., Reba, S. M., Harding, C. V., Boom, W. H. (2007). Modulation of Naive CD4+ T-Cell Responses to an Airway Antigen during Pulmonary Mycobacterial Infection. Infect. Immun. 75: 2260-2268 [Abstract] [Full Text]  
• Koch, M., Witzenrath, M., Reuter, C., Herma, M., Schutte, H., Suttorp, N., Collins, H., Kaufmann, S. H. E. (2006). Role of Local Pulmonary IFN-{gamma} Expression in Murine Allergic Airway Inflammation. Am. J. Respir. Cell Mol. Bio. 35: 211-219 [Abstract] [Full Text]  
• Kitagaki, K., Businga, T. R., Racila, D., Elliott, D. E., Weinstock, J. V., Kline, J. N. (2006). Intestinal Helminths Protect in a Murine Model of Asthma. J. Immunol. 177: 1628-1635 [Abstract] [Full Text]  
• Agea, E., Russano, A., Bistoni, O., Mannucci, R., Nicoletti, I., Corazzi, L., Postle, A. D., De Libero, G., Porcelli, S. A., Spinozzi, F. (2005). Human CD1-restricted T cell recognition of lipids from pollens. J. Exp. Med. 202: 295-308 [Abstract] [Full Text]  
• Gruber, C (2005). Childhood immunisations and the development of atopic disease. Arch. Dis. Child. 90: 553-555 [Full Text]  
• Peng, J.-K., Lin, J.-S., Kung, J. T., Finkelman, F. D., Wu-Hsieh, B. A. (2005). The combined effect of IL-4 and IL-10 suppresses the generation of, but does not change the polarity of, type-1 T cells in Histoplasma infection. Int Immunol 17: 193-205 [Abstract] [Full Text]  
• Mangan, N. E., Fallon, R. E., Smith, P., van Rooijen, N., McKenzie, A. N., Fallon, P. G. (2004). Helminth Infection Protects Mice from Anaphylaxis via IL-10-Producing B Cells. J. Immunol. 173: 6346-6356 [Abstract] [Full Text]  
• Radhakrishnan, S., Iijima, K., Kobayashi, T., Rodriguez, M., Kita, H., Pease, L. R. (2004). Blockade of Allergic Airway Inflammation Following Systemic Treatment with a B7-Dendritic Cell (PD-L2) Cross-Linking Human Antibody. J. Immunol. 173: 1360-1365 [Abstract] [Full Text]  
• Liesenfeld, O., Dunay, I. R., Erb, K. J. (2004). Infection with Toxoplasma gondii Reduces Established and Developing Th2 Responses Induced by Nippostrongylus brasiliensis Infection. Infect. Immun. 72: 3812-3822 [Abstract] [Full Text]  
• Marsland, B. J., Harris, N. L., Camberis, M., Kopf, M., Hook, S. M., Le Gros, G. (2004). Bystander suppression of allergic airway inflammation by lung resident memory CD8+ T cells. Proc. Natl. Acad. Sci. USA 101: 6116-6121 [Abstract] [Full Text]  
• Wohlleben, G., Trujillo, C., Muller, J., Ritze, Y., Grunewald, S., Tatsch, U., Erb, K. J. (2004). Helminth infection modulates the development of allergen-induced airway inflammation. Int Immunol 16: 585-596 [Abstract] [Full Text]  
• Branger, J., Leemans, J. C., Florquin, S., Weijer, S., Speelman, P., van der Poll, T. (2004). Toll-like receptor 4 plays a protective role in pulmonary tuberculosis in mice. Int Immunol 16: 509-516 [Abstract] [Full Text]  
• Erb, K. J., Twardzik, T., Palmetshofer, A., Wohlleben, G., Tatsch, U., Serfling, E. (2003). Mice Deficient in Nuclear Factor of Activated T-Cell Transcription Factor c2 Mount Increased Th2 Responses after Infection with Nippostrongylus brasiliensis and Decreased Th1 Responses after Mycobacterial Infection. Infect. Immun. 71: 6641-6647 [Abstract] [Full Text]  
• Lundy, S. K., Berlin, A. A., Lukacs, N. W. (2003). Interleukin-12-Independent Down-Modulation of Cockroach Antigen-Induced Asthma in Mice by Intranasal Exposure to Bacterial Lipopolysaccharide. Am. J. Pathol. 163: 1961-1968 [Abstract] [Full Text]  
• Chen, H. D., Fraire, A. E., Joris, I., Welsh, R. M., Selin, L. K. (2003). Specific History of Heterologous Virus Infections Determines Anti-Viral Immunity and Immunopathology in the Lung. Am. J. Pathol. 163: 1341-1355 [Abstract] [Full Text]  
• Chiang, D.-J., Ye, Y.-L., Chen, W.-L., Lee, Y.-L., Hsu, N.-Y., Chiang, B.-L. (2003). Ribavirin or CpG DNA Sequence-Modulated Dendritic Cells Decrease the IgE Level and Airway Inflammation. Am. J. Respir. Crit. Care Med. 168: 575-580 [Abstract] [Full Text]  
• Smit, J. J., Van Loveren, H., Hoekstra, M. O., Karimi, K., Folkerts, G., Nijkamp, F. P. (2003). The Slc11a1 (Nramp1) Gene Controls Efficacy of Mycobacterial Treatment of Allergic Asthma. J. Immunol. 171: 754-760 [Abstract] [Full Text]  
• Walzl, G., Humphreys, I. R., Marshall, B. G., Edwards, L., Openshaw, P. J. M., Shaw, R. J., Hussell, T. (2003). Prior Exposure to Live Mycobacterium bovis BCG Decreases Cryptococcus neoformans-Induced Lung Eosinophilia in a Gamma Interferon-Dependent Manner. Infect. Immun. 71: 3384-3391 [Abstract] [Full Text]  
• Wohlleben, G., Muller, J., Tatsch, U., Hambrecht, C., Herz, U., Renz, H., Schmitt, E., Moll, H., Erb, K. J. (2003). Influenza A Virus Infection Inhibits the Efficient Recruitment of Th2 Cells into the Airways and the Development of Airway Eosinophilia. J. Immunol. 170: 4601-4611 [Abstract] [Full Text]  
• Schramm, C., Herz, U., Podlech, J., Protschka, M., Finotto, S., Reddehase, M. J., Kohler, H., Galle, P. R., Lohse, A. W., Blessing, M. (2003). TGF-{beta} Regulates Airway Responses Via T Cells. J. Immunol. 170: 1313-1319 [Abstract] [Full Text]  
• Biet, F., Kremer, L., Wolowczuk, I., Delacre, M., Locht, C. (2002). Mycobacterium bovis BCG Producing Interleukin-18 Increases Antigen-Specific Gamma Interferon Production in Mice. Infect. Immun. 70: 6549-6557 [Abstract] [Full Text]  
• Rha, Y.-H., Taube, C., Haczku, A., Joetham, A., Takeda, K., Duez, C., Siegel, M., Aydintug, M. K., Born, W. K., Dakhama, A., Gelfand, E. W. (2002). Effect of Microbial Heat Shock Proteins on Airway Inflammation and Hyperresponsiveness. J. Immunol. 169: 5300-5307 [Abstract] [Full Text]  
• Hylkema, M. N., Timens, W., Luinge, M., van der Werf, N., Hoekstra, M. O. (2002). The Effect of Bacillus Calmette-Guerin Immunization Depends on the Genetic Predisposition to Th2-Type Responsiveness. Am. J. Respir. Cell Mol. Bio. 27: 244-249 [Abstract] [Full Text]  
• Zuany-Amorim, C., Manlius, C., Trifilieff, A., Brunet, L. R., 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 Allergic Pulmonary Inflammation. J. Immunol. 169: 1492-1499 [Abstract] [Full Text]  
• Erb, K. J., Trujillo, C., Fugate, M., Moll, H. (2002). Infection with the Helminth Nippostrongylus brasiliensis Does Not Interfere with Efficient Elimination of Mycobacterium bovis BCG from the Lungs of Mice. CVI 9: 727-730 [Abstract] [Full Text]  
• Dabbagh, K., Dahl, M. E., Stepick-Biek, P., Lewis, D. B. (2002). Toll-Like Receptor 4 Is Required for Optimal Development of Th2 Immune Responses: Role of Dendritic Cells. J. Immunol. 168: 4524-4530 [Abstract] [Full Text]  
• Hopfenspirger, M. T., Agrawal, D. K. (2002). Airway Hyperresponsiveness, Late Allergic Response, and Eosinophilia Are Reversed with Mycobacterial Antigens in Ovalbumin-Presensitized Mice. J. Immunol. 168: 2516-2522 [Abstract] [Full Text]  
• Renz, H., Herz, U. (2002). The bidirectional capacity of bacterial antigens to modulate allergy and asthma. Eur Respir J 19: 158-171 [Abstract] [Full Text]  
• Juffermans, N. P., Leemans, J. C., Florquin, S., Verbon, A., Kolk, A. H., Speelman, P., van Deventer, S. J. H., van der Poll, T. (2002). CpG Oligodeoxynucleotides Enhance Host Defense during Murine Tuberculosis. Infect. Immun. 70: 147-152 [Abstract] [Full Text]  
• Lipscomb, M. F., Masten, B. J. (2002). Dendritic Cells: Immune Regulators in Health and Disease. Physiol. Rev. 82: 97-130 [Abstract] [Full Text]  
• von Mutius, E. (2001). Infection: friend or foe in the development of atopy and asthma? The epidemiological evidence. Eur Respir J 18: 872-881 [Abstract] [Full Text]  
• Shibata, Y., Honda, I., Justice, J. P., Van Scott, M. R., Nakamura, R. M., Myrvik, Q. N. (2001). Th1 Adjuvant N-Acetyl-D-Glucosamine Polymer Up-Regulates Th1 Immunity but Down-Regulates Th2 Immunity against a Mycobacterial Protein (MPB-59) in Interleukin-10-Knockout and Wild-Type Mice. Infect. Immun. 69: 6123-6130 [Abstract] [Full Text]  
• Wong, G W K, Hui, D S C, Tam, C M, Chan, H H, Fok, T F, Chan-Yeung, M, Lai, C K W (2001). Asthma, atopy and tuberculin responses in Chinese schoolchildren in Hong Kong. Thorax 56: 770-773 [Abstract] [Full Text]  
• Gruber, C., Lau, S., Dannemann, A., Sommerfeld, C., Wahn, U., Aalberse, R. C. (2001). Down-Regulation of IgE and IgG4 Antibodies to Tetanus Toxoid and Diphtheria Toxoid by Covaccination with Cellular Bordetella pertussis Vaccine. J. Immunol. 167: 2411-2417 [Abstract] [Full Text]  
• SHIRTCLIFFE, P. M., EASTHOPE, S. E., CHENG, S., WEATHERALL, M., TAN, P. L. J., LE GROS, G., BEASLEY, R. (2001). The Effect of Delipidated Deglycolipidated (DDMV) and Heat-killed Mycobacterium vaccae in Asthma. Am. J. Respir. Crit. Care Med. 163: 1410-1414 [Abstract] [Full Text]  
• Leemans, J. C., Juffermans, N. P., Florquin, S., van Rooijen, N., Vervoordeldonk, M. J., Verbon, A., van Deventer, S. J. H., van der Poll, T. (2001). Depletion of Alveolar Macrophages Exerts Protective Effects in Pulmonary Tuberculosis in Mice. J. Immunol. 166: 4604-4611 [Abstract] [Full Text]  
• Mizuki, D., Miura, T., Sasaki, S., Mizuki, M., Madarame, H., Nakane, A. (2001). Interference between Host Resistance to Listeria monocytogenes Infection and Ovalbumin-Induced Allergic Responses in Mice. Infect. Immun. 69: 1883-1888 [Abstract] [Full Text]  
• Grüber, C., Kulig, M., Bergmann, R., Guggenmoos-Holzmann, I., Wahn, U., the MAS-90 Study Group, (2001). Delayed Hypersensitivity to Tuberculin, Total Immunoglobulin E, Specific Sensitization, and Atopic Manifestation in Longitudinally Followed Early Bacille Calmette-Guerin-Vaccinated and Nonvaccinated Children. Pediatrics 107: 36e-36 [Abstract] [Full Text]  
• Huang, T.-J., MacAry, P. A., Eynott, P., Moussavi, A., Daniel, K. C., Askenase, P. W., Kemeny, D. M., Chung, K. F. (2001). Allergen-Specific Th1 Cells Counteract Efferent Th2 Cell-Dependent Bronchial Hyperresponsiveness and Eosinophilic Inflammation Partly Via IFN-{{gamma}}. J. Immunol. 166: 207-217 [Abstract] [Full Text]  
• Walzl, G., Tafuro, S., Moss, P., Openshaw, P. J.M., Hussell, T. (2000). Influenza Virus Lung Infection Protects from Respiratory Syncytial Virus-induced Immunopathology. J. Exp. Med. 192: 1317-1326 [Abstract] [Full Text]  
• Lipford, G. B., Sparwasser, T., Zimmermann, S., Heeg, K., Wagner, H. (2000). CpG-DNA-Mediated Transient Lymphadenopathy Is Associated with a State of Th1 Predisposition to Antigen-Driven Responses. J. Immunol. 165: 1228-1235 [Abstract] [Full Text]  
• Miura, T., Mizuki, D., Sasaki, S., Hasegawa, S., Sashinami, H., Nakane, A. (2000). Host Resistance to Listeria monocytogenes Infection Is Enhanced but Resistance to Staphylococcus aureus Infection Is Reduced in Acute Graft-versus-Host Disease in Mice. Infect. Immun. 68: 4340-4343 [Abstract] [Full Text]  
• FUJIEDA, S., IHO, S., KIMURA, Y., YAMAMOTO, H., IGAWA, H., SAITO, H. (2000). Synthetic Oligodeoxynucleotides Inhibit IgE Induction in Human Lymphocytes. Am. J. Respir. Crit. Care Med. 162: 232-239 [Abstract] [Full Text]  
• von Mutius, E., Pearce, N., Beasley, R., Cheng, S., von Ehrenstein, O., Björkstén, B., Weiland, S. (2000). International patterns of tuberculosis and the prevalence of symptoms of asthma, rhinitis, and eczema. Thorax 55: 449-453 [Abstract] [Full Text]  
• von Hertzen, L. C., Haahtela, T. (2000). Could the Risk of Asthma and Atopy Be Reduced by a Vaccine That Induces a Strong T-helper Type 1 Response?. Am. J. Respir. Cell Mol. Bio. 22: 139-142 [Full Text]  
• Castro, M., Chaplin, D. D., Walter, M. J., Holtzman, M. J. (2000). Could Asthma Be Worsened by Stimulating the T-helper Type 1 Immune Response?. Am. J. Respir. Cell Mol. Bio. 22: 143-146 [Full Text]  
• Shirota, H., Sano, K., Kikuchi, T., Tamura, G., Shirato, K. (2000). Regulation of T-helper Type 2 Cell and Airway Eosinophilia by Transmucosal Coadministration of Antigen and Oligodeoxynucleotides Containing CpG Motifs. Am. J. Respir. Cell Mol. Bio. 22: 176-182 [Abstract] [Full Text]  
• Shibata, Y., Foster, L. A., Bradfield, J. F., Myrvik, Q. N. (2000). Oral Administration of Chitin Down-Regulates Serum IgE Levels and Lung Eosinophilia in the Allergic Mouse. J. Immunol. 164: 1314-1321 [Abstract] [Full Text]  
• Hansen, G., Yeung, V. P., Berry, G., Umetsu, D. T., DeKruyff, R. H. (2000). Vaccination with Heat-Killed Listeria as Adjuvant Reverses Established Allergen-Induced Airway Hyperreactivity and Inflammation: Role of CD8+ T Cells and IL-18. J. Immunol. 164: 223-230 [Abstract] [Full Text]  
• FUJIEDA, S., IHO, S., KIMURA, Y., SUNAGA, H., IGAWA, H., SUGIMOTO, C., YAMAMOTO, S., SAITO, H. (1999). DNA from Mycobacterium bovis Bacillus Calmette-Guerin (MY-1) Inhibits Immunoglobulin E Production by Human Lymphocytes. Am. J. Respir. Crit. Care Med. 160: 2056-2061 [Abstract] [Full Text]  
• Cohn, L., Homer, R. J., Niu, N., Bottomly, K. (1999). T Helper 1 Cells and Interferon {gamma} Regulate Allergic Airway Inflammation and Mucus Production. J. Exp. Med. 190: 1309-1318 [Abstract] [Full Text]  
• Donovan, C. E, Finn, P. W (1999). Immune mechanisms of childhood asthma. Thorax 54: 938-946 [Full Text]  
• Lee, N. A., Lee, J. J. (1999). The Macroimportance of the Pulmonary Immune Microenvironment. Am. J. Respir. Cell Mol. Bio. 21: 298-302 [Full Text]  
• Sano, K., Haneda, K., Tamura, G., Shirato, K. (1999). Ovalbumin (OVA) and Mycobacterium tuberculosis Bacilli Cooperatively Polarize Anti-OVA T-helper (Th) Cells toward a Th1-Dominant Phenotype and Ameliorate Murine Tracheal Eosinophilia. Am. J. Respir. Cell Mol. Bio. 20: 1260-1267 [Abstract] [Full Text]  
• Sur, S., Wild, J. S., Choudhury, B. K., Sur, N., Alam, R., Klinman, D. M. (1999). Long Term Prevention of Allergic Lung Inflammation in a Mouse Model of Asthma by CpG Oligodeoxynucleotides. J. Immunol. 162: 6284-6293 [Abstract] [Full Text]  
• Broide, D., Schwarze, J., Tighe, H., Gifford, T., Nguyen, M.-D., Malek, S., Van Uden, J., Martin-Orozco, E., Gelfand, E. W., Raz, E. (1998). Immunostimulatory DNA Sequences Inhibit IL-5, Eosinophilic Inflammation, and Airway Hyperresponsiveness in Mice. J. Immunol. 161: 7054-7062 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS