An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection

doi:10.1084/jem.178.6.2249

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An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection

JL Flynn, J Chan, KJ Triebold, DK Dalton, TA Stewart and BR Bloom
Howard Hughes Medical Institute, Department of Microbiology, Albert Einstein College of Medicine, Bronx, New York 10461.

Tuberculosis, a major health problem in developing countries, has reemerged in recent years in many industrialized countries. The increased susceptibility of immunocompromised individuals to tuberculosis, and many experimental studies indicate that T cell- mediated immunity plays an important role in resistance. The lymphokine interferon gamma (IFN-gamma) is thought to be a principal mediator of macrophage activation and resistance to intracellular pathogens. Mice have been developed which fail to produce IFN-gamma (gko), because of a targeted disruption of the gene for IFN-gamma. Upon infection with Mycobacterium tuberculosis, although they develop granulomas, gko mice fail to produce reactive nitrogen intermediates and are unable to restrict the growth of the bacilli. In contrast to control mice, gko mice exhibit heightened tissue necrosis and succumb to a rapid and fatal course of tuberculosis that could be delayed, but not prevented, by treatment with exogenous recombinant IFN-gamma.
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Page, K. R., Jedlicka, A. E., Fakheri, B., Noland, G. S., Kesavan, A. K., Scott, A. L., Kumar, N., Manabe, Y. C. (2005). Mycobacterium-Induced Potentiation of Type 1 Immune Responses and Protection against Malaria Are Host Specific. Infect. Immun. 73: 8369-8380 [Abstract] [Full Text]
Schierloh, P., Yokobori, N., Aleman, M., Musella, R. M., Beigier-Bompadre, M., Saab, M. A., Alves, L., Abbate, E., de la Barrera, S. S., Sasiain, M. C. (2005). Increased Susceptibility to Apoptosis of CD56dimCD16+ NK Cells Induces the Enrichment of IFN-{gamma}-Producing CD56bright Cells in Tuberculous Pleurisy. J. Immunol. 175: 6852-6860 [Abstract] [Full Text]
Kipnis, A., Irwin, S., Izzo, A. A., Basaraba, R. J., Orme, I. M. (2005). Memory T Lymphocytes Generated by Mycobacterium bovis BCG Vaccination Reside within a CD4 CD44lo CD62 Ligandhi Population. Infect. Immun. 73: 7759-7764 [Abstract] [Full Text]
Wieland, C. W., Florquin, S., Chan, E. D., Leemans, J. C., Weijer, S., Verbon, A., Fantuzzi, G., van der Poll, T. (2005). Pulmonary Mycobacterium tuberculosis infection in leptin-deficient ob/ob mice. Int Immunol 17: 1399-1408 [Abstract] [Full Text]
Maue, A. C., Waters, W. R., Davis, W. C., Palmer, M. V., Minion, F. C., Estes, D. M. (2005). Analysis of Immune Responses Directed toward a Recombinant Early Secretory Antigenic Target Six-Kilodalton Protein-Culture Filtrate Protein 10 Fusion Protein in Mycobacterium bovis-Infected Cattle. Infect. Immun. 73: 6659-6667 [Abstract] [Full Text]
Fukasawa, Y., Kawamura, I., Uchiyama, R., Yamamoto, K., Kaku, T., Tominaga, T., Nomura, T., Ichiyama, S., Ezaki, T., Mitsuyama, M. (2005). Streptomycin-Dependent Exhibition of Cytokine-Inducing Activity in Streptomycin-Dependent Mycobacterium tuberculosis Strain 18b. Infect. Immun. 73: 7051-7055 [Abstract] [Full Text]
Sullivan, B. M., Jobe, O., Lazarevic, V., Vasquez, K., Bronson, R., Glimcher, L. H., Kramnik, I. (2005). Increased Susceptibility of Mice Lacking T-bet to Infection with Mycobacterium tuberculosis Correlates with Increased IL-10 and Decreased IFN-{gamma} Production. J. Immunol. 175: 4593-4602 [Abstract] [Full Text]
Happel, K. I., Dubin, P. J., Zheng, M., Ghilardi, N., Lockhart, C., Quinton, L. J., Odden, A. R., Shellito, J. E., Bagby, G. J., Nelson, S., Kolls, J. K. (2005). Divergent roles of IL-23 and IL-12 in host defense against Klebsiella pneumoniae. JEM 202: 761-769 [Abstract] [Full Text]
Ordway, D., Henao-Tamayo, M., Orme, I. M., Gonzalez-Juarrero, M. (2005). Foamy Macrophages within Lung Granulomas of Mice Infected with Mycobacterium tuberculosis Express Molecules Characteristic of Dendritic Cells and Antiapoptotic Markers of the TNF Receptor-Associated Factor Family. J. Immunol. 175: 3873-3881 [Abstract] [Full Text]
Olsen, I., Boysen, P., Kulberg, S., Hope, J. C., Jungersen, G., Storset, A. K. (2005). Bovine NK Cells Can Produce Gamma Interferon in Response to the Secreted Mycobacterial Proteins ESAT-6 and MPP14 but Not in Response to MPB70. Infect. Immun. 73: 5628-5635 [Abstract] [Full Text]
Irwin, S. M., Izzo, A. A., Dow, S. W., Skeiky, Y. A. W., Reed, S. G., Alderson, M. R., Orme, I. M. (2005). Tracking Antigen-Specific CD8 T Lymphocytes in the Lungs of Mice Vaccinated with the Mtb72F Polyprotein. Infect. Immun. 73: 5809-5816 [Abstract] [Full Text]
Shin, S. J., Chang, C.-F., Chang, C.-D., McDonough, S. P., Thompson, B., Yoo, H. S., Chang, Y.-F. (2005). In Vitro Cellular Immune Responses to Recombinant Antigens of Mycobacterium avium subsp. paratuberculosis. Infect. Immun. 73: 5074-5085 [Abstract] [Full Text]
Matsumoto, S., Matsumoto, M., Umemori, K., Ozeki, Y., Furugen, M., Tatsuo, T., Hirayama, Y., Yamamoto, S., Yamada, T., Kobayashi, K. (2005). DNA Augments Antigenicity of Mycobacterial DNA-Binding Protein 1 and Confers Protection against Mycobacterium tuberculosis Infection in Mice. J. Immunol. 175: 441-449 [Abstract] [Full Text]
Simmons, C. P., Thwaites, G. E., Quyen, N. T. H., Chau, T. T. H., Mai, P. P., Dung, N. T., Stepniewska, K., White, N. J., Hien, T. T., Farrar, J. (2005). The Clinical Benefit of Adjunctive Dexamethasone in Tuberculous Meningitis Is Not Associated with Measurable Attenuation of Peripheral or Local Immune Responses. J. Immunol. 175: 579-590 [Abstract] [Full Text]
Gonzalez-Juarrero, M., Hattle, J. M., Izzo, A., Junqueira-Kipnis, A. P., Shim, T. S., Trapnell, B. C., Cooper, A. M., Orme, I. M. (2005). Disruption of granulocyte macrophage-colony stimulating factor production in the lungs severely affects the ability of mice to control Mycobacterium tuberculosis infection. J. Leukoc. Biol. 77: 914-922 [Abstract] [Full Text]
Samten, B., Howard, S. T., Weis, S. E., Wu, S., Shams, H., Townsend, J. C., Safi, H., Barnes, P. F. (2005). Cyclic AMP Response Element-Binding Protein Positively Regulates Production of IFN-{gamma} by T Cells in Response to a Microbial Pathogen. J. Immunol. 174: 6357-6363 [Abstract] [Full Text]