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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Spontaneous latency in a rabbit model of pulmonary tuberculosis
American Journal of Pathology, Volume 181, No. 5, Year 2012
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Description
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. © 2012 American Society for Investigative Pathology.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3483799/bin/mmc1.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC3483799/bin/mmc2.doc
Authors & Co-Authors
Subbian, Selvakumar
United States, Newark
Public Health Research Institute
Tsenova, Liana
United States, Newark
Public Health Research Institute
United States, New York
New York City College of Technology
O'Brien, Paul
United States, Newark
Public Health Research Institute
Yang, Guibin
United States, Newark
Public Health Research Institute
Kushner, Nicole
United States, Newark
Public Health Research Institute
Parsons, Sven D.C.
South Africa, Stellenbosch
Stellenbosch University
Peixoto, Blas
United States, Newark
Public Health Research Institute
Fallows, Dorothy A.
United States, Newark
Public Health Research Institute
Kaplan, Gilla
United States, Newark
Public Health Research Institute
Statistics
Citations: 55
Authors: 9
Affiliations: 3
Identifiers
Doi:
10.1016/j.ajpath.2012.07.019
e-ISSN:
15252191
Research Areas
Cancer
Infectious Diseases