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In vivo immunosuppressive activity of gliotoxin, a metabolite produced by human pathogenic fungi.

Division of Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra.

ABSTRACT

Aspergillosis is a disease caused by the opportunistic pathogen Aspergillus fumigatus and other related fungi. It occurs mainly in immunosuppressed people and causes very high mortality rates. A fumigatus and other pathogenic fungi have been shown to produce a metabolite, gliotoxin, which has immunosuppressive properties in vitro, but little is known about its in vivo activity. Here we report that gliotoxin has increased toxicity in mice after irradiation. A single injection of gliotoxin delayed the recovery of immune cells after immunosuppression by sublethal irradiation by 2 weeks. Study of the morphology of cells of the thymus, spleen, and mesenteric lymph nodes by light microscopy and electron microscopy and agarose gel electrophoresis of DNA from these organs showed that the injection of gliotoxin induced apoptosis in cells of the immune system in vivo. Thus, gliotoxin does have immunosuppressive activity in vivo and could potentially play a significant role in the pathogenesis of aspergillosis and other fungal diseases.

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