Journal article
Tumor Necrosis Factor Blockade in Chronic Murine Tuberculosis Enhances Granulomatous Inflammation and Disorganizes Granulomas in the Lungs
Infection and immunity, v 76(3), pp 916-926
01 Mar 2008
PMID: 18212087
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Tumor necrosis factor (TNF) is a prototypic proinflammatory cytokine that contributes significantly to the development of immunopathology in various disease states. A complication of TNF blockade therapy, which is used increasingly for the treatment of chronic inflammatory diseases, is the reactivation of latent tuberculosis. This study used a low-dose aerogenic model of murine tuberculosis to analyze the effect of TNF neutralization on disease progression in mice with chronic tuberculous infections. Histological, immunohistochemical, and flow cytometric analyses of
Mycobacterium tuberculosis
-infected lung tissues revealed that the neutralization of TNF results in marked disorganization of the tuberculous granuloma, as demonstrated by the dissolution of the previously described B-cell-macrophage unit in granulomatous tissues as well as by increased inflammatory cell infiltration. Quantitative gene expression studies using laser capture microdissected granulomatous lung tissues revealed that TNF blockade in mice chronically infected with
M. tuberculosis
leads to the enhanced expression of specific proinflammatory molecules. Collectively, these studies have provided evidence suggesting that in the chronic phase of
M. tuberculosis
infection, TNF is essential for maintaining the structure of the tuberculous granuloma and may regulate the granulomatous response by exerting an anti-inflammatory effect through modulation of the expression of proinflammatory mediators.
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Details
- Title
- Tumor Necrosis Factor Blockade in Chronic Murine Tuberculosis Enhances Granulomatous Inflammation and Disorganizes Granulomas in the Lungs
- Creators
- Soumya D. Chakravarty - University of Michigan–Ann ArborGuofeng Zhu - Albert Einstein College of MedicineMing C. Tsai - University of Michigan–Ann ArborVellore P. Mohan - Montefiore Medical CenterSimeone Marino - University of Michigan–Ann ArborDenise E. Kirschner - University of Michigan–Ann ArborLuqi Huang - Chinese Academy of Medical Sciences & Peking Union Medical CollegeJoAnne Flynn - University of PittsburghJohn Chan - Albert Einstein College of Medicine
- Publication Details
- Infection and immunity, v 76(3), pp 916-926
- Publisher
- American Society for Microbiology (ASM)
- Number of pages
- 11
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Rheumatology; General Internal Medicine
- Web of Science ID
- WOS:000253563500007
- Scopus ID
- 2-s2.0-40749108974
- Other Identifier
- 991021930317504721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology
- Infectious Diseases