Effects of tumor necrosis factor alpha on host immune response in chronic persistent tuberculosis: Possible role for limiting pathology

V. P. Mohan, C. A. Scanga, K. Yu, H. M. Scott, Kathryn E. Tanaka, E. Tsang, M. C. Tsai, J. L. Flynn, John Chan

Research output: Contribution to journalArticle

386 Citations (Scopus)

Abstract

Reactivation of latent tuberculosis contributes significantly to the incidence of disease caused by Mycobacterium tuberculosis. The mechanisms involved in the containment of latent tuberculosis are poorly understood. Using the low-dose model of persistent murine tuberculosis in conjunction with MP6-XT22, a monoclonal antibody that functionally neutralizes tumor necrosis factor alpha (TNF-α), we examined the effects of TNF-α on the immunological response of the host in both persistent and reactivated tuberculous infections. The results confirm an essential role for TNF-α in the containment of persistent tuberculosis. TNF-α neutralization resulted in fatal reactivation of persistent tuberculosis characterized by a moderately increased tissue bacillary burden and severe pulmonic histopathological deterioration that was associated with changes indicative of squamous metaplasia and fluid accumulation in the alveolar space. Analysis of pulmonic gene and protein expression of mice in the low-dose model revealed that nitric oxide synthase was attenuated during MP6-XT22-induced reactivation, but was not totally suppressed. Interleukin-12p40 and gamma interferon gene expression in TNF-α-neutralized mice was similar to that in control mice. In contrast, interleukin-10 expression was augmented in the TNF-α-neutralized mice. In summary, results of this study suggest that TNF-α plays an essential role in preventing reactivation of persistent tuberculosis, modulates the pulmonic expression of specific immunologic factors, and limits the pathological response of the host.

Original languageEnglish (US)
Pages (from-to)1847-1855
Number of pages9
JournalInfection and Immunity
Volume69
Issue number3
DOIs
StatePublished - 2001
Externally publishedYes

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Tuberculosis
Tumor Necrosis Factor-alpha
Pathology
Latent Tuberculosis
Lung
Gene Expression
Interleukins
Metaplasia
Immunologic Factors
Mycobacterium tuberculosis
Nitric Oxide Synthase
Interleukin-10
Interferon-gamma
Monoclonal Antibodies
Incidence
Infection
Proteins

ASJC Scopus subject areas

  • Immunology

Cite this

Effects of tumor necrosis factor alpha on host immune response in chronic persistent tuberculosis : Possible role for limiting pathology. / Mohan, V. P.; Scanga, C. A.; Yu, K.; Scott, H. M.; Tanaka, Kathryn E.; Tsang, E.; Tsai, M. C.; Flynn, J. L.; Chan, John.

In: Infection and Immunity, Vol. 69, No. 3, 2001, p. 1847-1855.

Research output: Contribution to journalArticle

Mohan, V. P. ; Scanga, C. A. ; Yu, K. ; Scott, H. M. ; Tanaka, Kathryn E. ; Tsang, E. ; Tsai, M. C. ; Flynn, J. L. ; Chan, John. / Effects of tumor necrosis factor alpha on host immune response in chronic persistent tuberculosis : Possible role for limiting pathology. In: Infection and Immunity. 2001 ; Vol. 69, No. 3. pp. 1847-1855.
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