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Spontaneous latency in a rabbit model of pulmonary tuberculosis.

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.
AuthorsSelvakumar Subbian, Liana Tsenova, Paul O'Brien, Guibin Yang, Nicole L Kushner, Sven Parsons, Blas Peixoto, Dorothy Fallows, Gilla Kaplan
JournalThe American journal of pathology (Am J Pathol) Vol. 181 Issue 5 Pg. 1711-24 (Nov 2012) ISSN: 1525-2191 [Electronic] United States
PMID22960076 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Topics
  • Animals
  • Bacterial Load (immunology)
  • Cell Proliferation
  • Disease Models, Animal
  • Female
  • Flow Cytometry
  • Gene Expression Profiling
  • Humans
  • Latent Tuberculosis (genetics, immunology, microbiology, pathology)
  • Lung (immunology, microbiology, pathology)
  • Lymphocyte Activation (genetics, immunology)
  • Macrophage Activation (genetics, immunology)
  • Mycobacterium tuberculosis (growth & development)
  • Pulmonary Fibrosis (genetics, microbiology, pathology)
  • Rabbits
  • Signal Transduction (genetics)
  • Spleen (immunology, microbiology)
  • T-Lymphocytes (immunology)
  • Transcription, Genetic
  • Tuberculosis, Pulmonary (genetics, immunology, microbiology, pathology)

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