This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Scanga, C. A.
Right arrow Articles by Flynn, J. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Scanga, C. A.
Right arrow Articles by Flynn, J. L.

 Previous Article  |  Next Article 

Infection and Immunity, September 1999, p. 4531-4538, Vol. 67, No. 9
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Reactivation of Latent Tuberculosis: Variations on the Cornell Murine Model

Charles A. Scanga,1 V. P. Mohan,2 Heather Joseph,1 Keming Yu,2 John Chan,2,3 and JoAnne L. Flynn1,*

Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261,1 and Departments of Microbiology and Immunology2 and of Medicine,3 Albert Einstein College of Medicine, Bronx, New York 10467

Received 16 February 1999/Returned for modification 17 March 1999/Accepted 14 June 1999

Mycobacterium tuberculosis causes active tuberculosis in only a small percentage of infected persons. In most cases, the infection is clinically latent, although immunosuppression can cause reactivation of a latent M. tuberculosis infection. Surprisingly little is known about the biology of the bacterium or the host during latency, and experimental studies on latent tuberculosis suffer from a lack of appropriate animal models. The Cornell model is a historical murine model of latent tuberculosis, in which mice infected with M. tuberculosis are treated with antibiotics (isoniazid and pyrazinamide), resulting in no detectable bacilli by organ culture. Reactivation of infection during this culture-negative state occurred spontaneously and following immunosuppression. In the present study, three variants of the Cornell model were evaluated for their utility in studies of latent and reactivated tuberculosis. The antibiotic regimen, inoculating dose, and antibiotic-free rest period prior to immunosuppression were varied. A variety of immunosuppressive agents, based on immunologic factors known to be important to control of acute infection, were used in attempts to reactivate the infection. Although reactivation of latent infection was observed in all three variants, these models were associated with characteristics that limit their experimental utility, including spontaneous reactivation, difficulties in inducing reactivation, and the generation of altered bacilli. The results from these studies demonstrate that the outcome of Cornell model-based studies depends critically upon the parameters used to establish the model.

* Corresponding author. Mailing address: Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261. Phone: (412) 624-7743. Fax: (412) 624-1401. E-mail: joanne{at}pop.pitt.edu.

Infection and Immunity, September 1999, p. 4531-4538, Vol. 67, No. 9
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Windish, H. P., Lin, P. L., Mattila, J. T., Green, A. M., Onuoha, E. O., Kane, L. P., Flynn, J. L. (2009). Aberrant TGF-{beta} signaling reduces T regulatory cells in ICAM-1-deficient mice, increasing the inflammatory response to Mycobacterium tuberculosis. J. Leukoc. Biol. 86: 713-725 [Abstract] [Full Text]  
  • Cirillo, S. L. G., Subbian, S., Chen, B., Weisbrod, T. R., Jacobs, W. R. 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: 2557-2567 [Abstract] [Full Text]  
  • Woolhiser, L. K., Hoff, D. R., Marietta, K. S., Orme, I. M., Lenaerts, A. J. (2009). Testing of Experimental Compounds in a Relapse Model of Tuberculosis Using Granulocyte-Macrophage Colony-Stimulating Factor Gene-Disrupted Mice. Antimicrob. Agents Chemother. 53: 306-308 [Abstract] [Full Text]  
  • Dharmadhikari, A. S., Nardell, E. A. (2008). What Animal Models Teach Humans about Tuberculosis. Am. J. Respir. Cell Mol. Bio. 39: 503-508 [Abstract] [Full Text]  
  • Russell-Goldman, E., Xu, J., Wang, X., Chan, J., Tufariello, J. M. (2008). A Mycobacterium tuberculosis Rpf Double-Knockout Strain Exhibits Profound Defects in Reactivation from Chronic Tuberculosis and Innate Immunity Phenotypes. Infect. Immun. 76: 4269-4281 [Abstract] [Full Text]  
  • Pandey, A. K., Sassetti, C. M. (2008). Mycobacterial persistence requires the utilization of host cholesterol. Proc. Natl. Acad. Sci. USA 105: 4376-4380 [Abstract] [Full Text]  
  • Hett, E. C., Rubin, E. J. (2008). Bacterial Growth and Cell Division: a Mycobacterial Perspective. Microbiol. Mol. Biol. Rev. 72: 126-156 [Abstract] [Full Text]  
  • Chakravarty, S. D., Zhu, G., Tsai, M. C., Mohan, V. P., Marino, S., Kirschner, D. E., Huang, L., Flynn, J., Chan, J. (2008). Tumor Necrosis Factor Blockade in Chronic Murine Tuberculosis Enhances Granulomatous Inflammation and Disorganizes Granulomas in the Lungs. Infect. Immun. 76: 916-926 [Abstract] [Full Text]  
  • Lawley, T. D., Bouley, D. M., Hoy, Y. E., Gerke, C., Relman, D. A., Monack, D. M. (2008). Host Transmission of Salmonella enterica Serovar Typhimurium Is Controlled by Virulence Factors and Indigenous Intestinal Microbiota. Infect. Immun. 76: 403-416 [Abstract] [Full Text]  
  • Talaat, A. M., Ward, S. K., Wu, C.-W., Rondon, E., Tavano, C., Bannantine, J. P., Lyons, R., Johnston, S. A. (2007). Mycobacterial Bacilli Are Metabolically Active during Chronic Tuberculosis in Murine Lungs: Insights from Genome-Wide Transcriptional Profiling. J. Bacteriol. 189: 4265-4274 [Abstract] [Full Text]  
  • Woolhiser, L., Tamayo, M. H., Wang, B., Gruppo, V., Belisle, J. T., Lenaerts, A. J., Basaraba, R. J., Orme, I. M. (2007). In Vivo Adaptation of the Wayne Model of Latent Tuberculosis. Infect. Immun. 75: 2621-2625 [Abstract] [Full Text]  
  • Sawant, K. V., McMurray, D. N. (2007). Guinea Pig Neutrophils Infected with Mycobacterium tuberculosis Produce Cytokines Which Activate Alveolar Macrophages in Noncontact Cultures. Infect. Immun. 75: 1870-1877 [Abstract] [Full Text]  
  • Davies, G. R., Pym, A. S., Mitchison, D. A., Nuermberger, E. L., Grosset, J. H. (2007). Evaluation of New Antituberculosis Drugs in Mouse Models. Antimicrob. Agents Chemother. 51: 403-404 [Full Text]  
  • Kamath, A. B., Behar, S. M. (2005). Anamnestic Responses of Mice following Mycobacterium tuberculosis Infection. Infect. Immun. 73: 6110-6118 [Abstract] [Full Text]  
  • Dubnau, E., Chan, J., Mohan, V. P., Smith, I. (2005). Responses of Mycobacterium tuberculosis to Growth in the Mouse Lung. Infect. Immun. 73: 3754-3757 [Abstract] [Full Text]  
  • Lazarevic, V., Yankura, D. J., Divito, S. J., Flynn, J. L. (2005). Induction of Mycobacterium tuberculosis-Specific Primary and Secondary T-Cell Responses in Interleukin-15-Deficient Mice. Infect. Immun. 73: 2910-2922 [Abstract] [Full Text]  
  • Feng, C. G., Jankovic, D., Kullberg, M., Cheever, A., Scanga, C. A., Hieny, S., Caspar, P., Yap, G. S., Sher, A. (2005). Maintenance of Pulmonary Th1 Effector Function in Chronic Tuberculosis Requires Persistent IL-12 Production. J. Immunol. 174: 4185-4192 [Abstract] [Full Text]  
  • Buettner, M., Meinken, C., Bastian, M., Bhat, R., Stossel, E., Faller, G., Cianciolo, G., Ficker, J., Wagner, M., Rollinghoff, M., Stenger, S. (2005). Inverse Correlation of Maturity and Antibacterial Activity in Human Dendritic Cells. J. Immunol. 174: 4203-4209 [Abstract] [Full Text]  
  • Cho, H., Lasco, T. M., Allen, S. S., Yoshimura, T., McMurray, D. N. (2005). Recombinant Guinea Pig Tumor Necrosis Factor Alpha Stimulates the Expression of Interleukin-12 and the Inhibition of Mycobacterium tuberculosis Growth in Macrophages. Infect. Immun. 73: 1367-1376 [Abstract] [Full Text]  
  • Algood, H. M. S., Lin, P. L., Yankura, D., Jones, A., Chan, J., Flynn, J. L. (2004). TNF Influences Chemokine Expression of Macrophages In Vitro and That of CD11b+ Cells In Vivo during Mycobacterium tuberculosis Infection. J. Immunol. 172: 6846-6857 [Abstract] [Full Text]  
  • Monack, D. M., Bouley, D. M., Falkow, S. (2004). Salmonella typhimurium Persists within Macrophages in the Mesenteric Lymph Nodes of Chronically Infected Nramp1+/+ Mice and Can Be Reactivated by IFN{gamma} Neutralization. JEM 199: 231-241 [Abstract] [Full Text]  
  • Botha, T., Ryffel, B. (2003). Reactivation of Latent Tuberculosis Infection in TNF-Deficient Mice. J. Immunol. 171: 3110-3118 [Abstract] [Full Text]  
  • Taylor, J. L., Turner, O. C., Basaraba, R. J., Belisle, J. T., Huygen, K., Orme, I. M. (2003). Pulmonary Necrosis Resulting from DNA Vaccination against Tuberculosis. Infect. Immun. 71: 2192-2198 [Abstract] [Full Text]  
  • Repique, C. J., Li, A., Collins, F. M., Morris, S. L. (2002). DNA Immunization in a Mouse Model of Latent Tuberculosis: Effect of DNA Vaccination on Reactivation of Disease and on Reinfection with a Secondary Challenge. Infect. Immun. 70: 3318-3323 [Abstract] [Full Text]  
  • Flynn, J. L., Chan, J. (2001). Tuberculosis: Latency and Reactivation. Infect. Immun. 69: 4195-4201 [Full Text]  
  • Serbina, N. V., Flynn, J. L. (2001). CD8+ T Cells Participate in the Memory Immune Response to Mycobacterium tuberculosis. Infect. Immun. 69: 4320-4328 [Abstract] [Full Text]  
  • Mohan, V. P., Scanga, C. A., Yu, K., Scott, H. M., Tanaka, K. E., Tsang, E., Tsai, M. C., Flynn, J. L., Chan, J. (2001). Effects of Tumor Necrosis Factor Alpha on Host Immune Response in Chronic Persistent Tuberculosis: Possible Role for Limiting Pathology. Infect. Immun. 69: 1847-1855 [Abstract] [Full Text]  
  • Scanga, C. A., Mohan, V.P., Yu, K., Joseph, H., Tanaka, K., Chan, J., Flynn, J. L. (2000). Depletion of Cd4+ T Cells Causes Reactivation of Murine Persistent Tuberculosis despite Continued Expression of Interferon {gamma} and Nitric Oxide Synthase 2. JEM 192: 347-358 [Abstract] [Full Text]  
  • Turner, O. C., Roberts, A. D., Frank, A. A., Phalen, S. W., McMurray, D. M., Content, J., Denis, O., D'Souza, S., Tanghe, A., Huygen, K., Orme, I. M. (2000). Lack of Protection in Mice and Necrotizing Bronchointerstitial Pneumonia with Bronchiolitis in Guinea Pigs Immunized with Vaccines Directed against the hsp60 Molecule of Mycobacterium tuberculosis. Infect. Immun. 68: 3674-3679 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»