Previous Article | Next Article 
Infection and Immunity, October 2009, p. 4631-4642, Vol. 77, No. 10
0019-9567/09/$08.00+0 doi:10.1128/IAI.00592-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Quantitative Comparison of Active and Latent Tuberculosis in the Cynomolgus Macaque Model
,
Philana Ling Lin,1
Mark Rodgers,2
Le'kneitah Smith,2
Matthew Bigbee,2
Amy Myers,2
Carolyn Bigbee,2
Ion Chiosea,2
Saverio V. Capuano,2,5,
Carl Fuhrman,3
Edwin Klein,4 and
JoAnne L. Flynn2*
Department of Pediatrics, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15224,1 Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261,2 Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15261,3 Division of Laboratory Animal Resources, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261,4 Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 152615
Received 27 May 2009/ Returned for modification 9 July 2009/ Accepted 15 July 2009
We previously described that low-dose Mycobacterium tuberculosis infection in cynomolgus macaques results in a spectrum of disease similar to that of human infection: primary disease, latent infection, and reactivation tuberculosis (S. V. Capuano III, D. A. Croix, S. Pawar, A. Zinovik, A. Myers, P. L. Lin, S. Bissel, C. Fuhrman, E. Klein, and J. L. Flynn, Infect. Immun. 71:5831-5844, 2003). This is the only established model of latent infection, and it provides a unique opportunity to understand host and pathogen differences across of range of disease states. Here, we provide a more extensive and detailed characterization of the gross pathology, microscopic histopathology, and immunologic characteristics of monkeys in each clinical disease category. The data underscore the similarities between human and nonhuman primate M. tuberculosis infection. Furthermore, we describe novel methods of quantifying gross pathology and bacterial burden that distinguish between active disease and latent infection, and we extend the usefulness of this model for comparative studies. Early in infection, an abnormal chest X ray, M. tuberculosis growth by gastric aspirate, and increased mycobacterium-specific gamma interferon (IFN-
) in peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage (BAL) cells were associated with the development of active disease. At necropsy, disease was quantified with respect to pathology and bacterial numbers. Microscopically, a spectrum of granuloma types are seen and differ with disease type. At necropsy, monkeys with active disease had more lung T cells and more IFN- from PBMC, BAL, and mediastinal lymph nodes than monkeys with latent infection. Finally, we have observed a spectrum of disease not only in monkeys with active disease but also in those with latent infection that provides insight into human latent tuberculosis.
* Corresponding author. Mailing address: W1144 Biomedical Science Tower, Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261. Phone: (412) 624-8664. Fax: (412) 648-3394. E-mail: joanne{at}pitt.edu
Published ahead of print on 20 July 2009.
Supplemental material for this article may be found at http://iai.asm.org/.
Present address: Wisconsin National Primate Research Center, Madison, WI 53715.
Infection and Immunity, October 2009, p. 4631-4642, Vol. 77, No. 10
0019-9567/09/$08.00+0 doi:10.1128/IAI.00592-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Copyright © 2009 by the American Society for Microbiology. For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»