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Updated: Aug 14, 2026

Assessing Anti-fungal Activity of Isolated Alveolar Macrophages by Confocal Microscopy
Published on: July 10, 2014
Contribution of tumour necrosis factor-alpha (TNF-alpha) in host defence mechanism against Cryptococcus neoformans
K Kawakami1, X Qifeng, M Tohyama
1First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
Abstract:
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.
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