Evaluating the role of tumor necrosis factor-alpha in experimental pulmonary tuberculosis in the guinea pig

Todd M. Lasco, Lynne Cassone, Hidenobu Kamohara, Teizo Yoshimura, David N. McMurray

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

Tumor necrosis factor-α (TNF-α) is suggested to play multiple roles in immune and pathologic responses in tuberculosis. In this study, we have developed a system for the expression of recombinant guinea pig TNF-α (rgpTNF-α). Using rgpTNF-α along with neutralizing anti-rgpTNF-α antiserum, we tested the effect of modulating the levels of TNF-α on antigen-specific T cell proliferation in splenocytes. By neutralizing TNF-α in the supernatant of PPD-pulsed splenocytes with anti-rgpTNF-α, we observed hyperproliferation. Conversely, the addition of rgpTNF-α resulted in a significant suppression of PPD-induced lymphoproliferation. In addition, when unvaccinated and BCG-vaccinated guinea pigs were treated with polyclonal rgpTNF-α antiserum throughout the first 3 weeks following low-dose, pulmonary infection with Mycobacterium tuberculosis H37Rv, we observed splenomegaly in BCG-vaccinated guinea pigs. We also detected higher levels of splenic granuloma organization in the non-vaccinated group as well as a significant number of plasma cells associated with granulomata from the BCG-vaccinated group. These results suggest that modulating the availability of TNF-α in BCG-vaccinated guinea pigs can lead to immuno-dysregulation and, perhaps, the inappropriate enhancement of humoral immunity. Conversely, abrogating TNF-α activity in the context of a hyperinflammatory response in non-vaccinated guinea pigs may, in fact, rescue them from immunopathological consequences of overproducing TNF-α.

Original languageEnglish
Pages (from-to)245-258
Number of pages14
JournalTuberculosis
Volume85
Issue number4
DOIs
Publication statusPublished - Jul 1 2005
Externally publishedYes

Keywords

  • Granuloma
  • Guinea pig
  • Mycobacterium tuberculosis
  • TNF-α

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

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