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

K. Kawakami, X. Qifeng, M. Tohyama, M. H. Qureshi, A. Saito

Research output: Contribution to journalArticlepeer-review

64 Citations (Scopus)

Abstract

We investigated the role of TNF-α in the host defence mechanism against infection with a virulent strain of Cryptococcus neoformans. Administration of exogenous recombinant human TNF-α significantly prolonged the survival time of mice infected by intratracheal instillation of the organism. Surprisingly, neutralizing MoAb to murine TNF-α 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-α in the lungs of infected mice. During the course of cryptococcosis, there was little or no generation of TNF-αmRNA in the lung. This might be partly due to a direct inhibitory action of the fungal microorganism on TNF-α production by macrophages. In vitro production of TNF-α by murine interferon-gamma (IFN-γ)- 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-α production and the neutralizing anti-TNF-α MoAb strongly blocked IL-12-induced protection of mice against cryptococcal infection. These results indicate that endogenously synthesized TNF-α has the potential to contribute to the elimination of C. neoformans and partly mediates the protective effect of IL-12.

Original languageEnglish
Pages (from-to)468-474
Number of pages7
JournalClinical and Experimental Immunology
Volume106
Issue number3
DOIs
Publication statusPublished - 1996
Externally publishedYes

Keywords

  • Cryptococcus neoformans
  • IL-12
  • Macrophages
  • Tumour necrosis factor-alpha

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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