Quantitative comparison of active and latent tuberculosis in the cynomolgus macaque model.
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-gamma) 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-gamma 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.
Lin
Philana Ling
PL
Department of Pediatrics, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15224, USA.
Rodgers
Mark
M
Smith
Le'kneitah
L
Bigbee
Matthew
M
Myers
Amy
A
Bigbee
Carolyn
C
Chiosea
Ion
I
Capuano
Saverio V
SV
Fuhrman
Carl
C
Klein
Edwin
E
Flynn
JoAnne L
JL
D000818:Animals; D001769:Blood / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D006099:Granuloma / Q000473:pathology; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008198:Lymph Nodes / Q000382:microbiology / Q000473:pathology; D008252:Macaca fascicularis; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D013902:Radiography, Thoracic; D012720:Severity of Illness Index; D013270:Stomach / Q000382:microbiology; D014376:Tuberculosis / Q000276:immunology* / Q000473:pathology*
D007371:Interferon-gamma