Contribution of tumour necrosis factor-alpha (TNF-alpha) in host defence mechanism against Cryptococcus neoformans

Clin Exp Immunol. 1996 Dec;106(3):468-74. doi: 10.1046/j.1365-2249.1996.d01-870.x.


We investigated the role of TNF-alpha in the host defence mechanism against infection with a virulent strain of Cryptococcus neoformans. Administration of exogenous recombinant human TNF-alpha significantly prolonged the survival time of mice infected by intratracheal instillation of the organism. Surprisingly, neutralizing MoAb to murine TNF-alpha did not shorten their survival time, a finding inconsistent with previous results. To investigate the cause of this inconsistency, we examined the production of TNF-alpha in the lungs of infected mice. During the course of cryptococcosis, there was little or no generation of TNF-alpha mRNA in the lung. This might be partly due to a direct inhibitory action of the fungal microorganism of TNF-alpha production by macrophages. In vitro production of TNF-alpha by murine interferon-gamma (IFN-gamma)- and lipopolysaccharide (LPS)-stimulated macrophages was strongly inhibited by co-culturing with the whole yeast cells. In contrast, administration of recombinant murine IL-12 markedly induced TNF-alpha production and the neutralizing anti-TNF-alpha MoAb strongly blocked IL-12-induced protection of mice against cryptococcal infection. These results indicate that endogenously synthesized TNF-alpha has the potential to contribute to the elimination of C. neoformans and partly mediates the protective effect of IL-12.

MeSH terms

  • Animals
  • Antibodies, Fungal / immunology
  • Binding, Competitive / immunology
  • Cryptococcosis / diagnosis
  • Cryptococcosis / immunology*
  • Female
  • Humans
  • Interferon-gamma / immunology
  • Interleukin-12 / immunology
  • Lipopolysaccharides / immunology
  • Lung / metabolism
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred DBA
  • Prognosis
  • RNA, Messenger / analysis
  • Recombinant Proteins / immunology
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology*


  • Antibodies, Fungal
  • Lipopolysaccharides
  • RNA, Messenger
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Interleukin-12
  • Interferon-gamma