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Spontaneous latency in a rabbit model of pulmonary tuberculosis.
- Source :
-
The American journal of pathology [Am J Pathol] 2012 Nov; Vol. 181 (5), pp. 1711-24. Date of Electronic Publication: 2012 Sep 05. - Publication Year :
- 2012
-
Abstract
- Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is an exquisitely adapted human pathogen capable of surviving for decades in the lungs of immune-competent individuals in the absence of disease. The World Health Organization estimates that 2 billion people have latent TB infection (LTBI), defined by a positive immunological response to Mtb antigens, with no clinical signs of disease. A better understanding of host and pathogen determinants of LTBI and subsequent reactivation would benefit TB control efforts. Animal models of LTBI have been hampered generally by an inability to achieve complete bacillary clearance. Herein, we have characterized a rabbit model of LTBI in which, similar to most humans, complete clearance of pulmonary Mtb infection and pathological characteristics occurs spontaneously. The evidence that Mtb-CDC1551-infected rabbits achieve LTBI, rather than sterilization, is based on the ability of the bacilli to be reactivated after immune suppression. These rabbits showed early activation of T cells and macrophages and an early peak in the TNFα level, which decreased in association with clearance of bacilli from the lungs. In the absence of sustained tumor necrosis factor-α production, no necrosis was seen in the evolving lung granulomas. In addition, bacillary control was associated with down-regulation of several metalloprotease genes and an absence of lung fibrosis. This model will be used to characterize molecular markers of protective immunity and reactivation.<br /> (Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Bacterial Load immunology
Cell Proliferation
Disease Models, Animal
Female
Flow Cytometry
Gene Expression Profiling
Humans
Latent Tuberculosis genetics
Latent Tuberculosis microbiology
Latent Tuberculosis pathology
Lung immunology
Lung microbiology
Lung pathology
Lymphocyte Activation genetics
Lymphocyte Activation immunology
Macrophage Activation genetics
Macrophage Activation immunology
Mycobacterium tuberculosis growth & development
Pulmonary Fibrosis genetics
Pulmonary Fibrosis microbiology
Pulmonary Fibrosis pathology
Rabbits
Signal Transduction genetics
Spleen immunology
Spleen microbiology
T-Lymphocytes immunology
Transcription, Genetic
Tuberculosis, Pulmonary genetics
Tuberculosis, Pulmonary microbiology
Tuberculosis, Pulmonary pathology
Latent Tuberculosis immunology
Tuberculosis, Pulmonary immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1525-2191
- Volume :
- 181
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- The American journal of pathology
- Publication Type :
- Academic Journal
- Accession number :
- 22960076
- Full Text :
- https://doi.org/10.1016/j.ajpath.2012.07.019