Tumor necrosis factor blockade in chronic murine tuberculosis enhances granulomatous inflammation and disorganizes granulomas in the lungs

Soumya D. Chakravarty, Guofeng Zhu, Ming C. Tsai, Vellore P. Mohan, Simeone Marino, Denise E. Kirschner, Luqi Huang, JoAnne Flynn, John Chan

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)916-926
Number of pages11
JournalInfection and Immunity
Volume76
Issue number3
DOIs
StatePublished - Mar 2008

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Granuloma
Tuberculosis
Tumor Necrosis Factor-alpha
Inflammation
Lung
Mycobacterium tuberculosis
Latent Tuberculosis
Mycobacterium Infections
Disease Progression
Lasers
B-Lymphocytes
Chronic Disease
Anti-Inflammatory Agents
Macrophages
Cytokines
Gene Expression
Infection

ASJC Scopus subject areas

  • Immunology

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Tumor necrosis factor blockade in chronic murine tuberculosis enhances granulomatous inflammation and disorganizes granulomas in the lungs. / Chakravarty, Soumya D.; Zhu, Guofeng; Tsai, Ming C.; Mohan, Vellore P.; Marino, Simeone; Kirschner, Denise E.; Huang, Luqi; Flynn, JoAnne; Chan, John.

In: Infection and Immunity, Vol. 76, No. 3, 03.2008, p. 916-926.

Research output: Contribution to journalArticle

Chakravarty, Soumya D. ; Zhu, Guofeng ; Tsai, Ming C. ; Mohan, Vellore P. ; Marino, Simeone ; Kirschner, Denise E. ; Huang, Luqi ; Flynn, JoAnne ; Chan, John. / Tumor necrosis factor blockade in chronic murine tuberculosis enhances granulomatous inflammation and disorganizes granulomas in the lungs. In: Infection and Immunity. 2008 ; Vol. 76, No. 3. pp. 916-926.
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