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Immunosuppressive Action Of Fungal Metabolite - Gliotoxin

Researchers from Japan have recently demonstrated the first evidence that mast cell is a direct target of gliotoxin.

Fungal secondary metabolites such as gliotoxin, an epipolythiodioxopiperazine toxin produced by pathogenic fungi like Candida and Aspergillus//, possess immunosuppressive activities and have been thought to contribute to pathology of fungal infections in animals and humans.

Mast cells play a key role in host defense and are important both for innate and adaptive immunity, and so, these findings suggest that suppression of mast cell activation might contribute to the establishment of infections for the pathogenic gliotoxin-producing fungi. Since recent studies show that mast cell plays a crucial role in the front of host defense, researchers examined whether fungal secondary metabolites affected mast cell activation.

Their study findings appear in the journal Clinical Immunology (available online 6 October 2005) The researchers found that gliotoxin had suppressive effects on mast cell activation, including degranulation, leukotriene C4 secretion, and TNF-á and IL-13 production. Gliotoxin also suppressed intracellular Ca2+ rise through store-operated Ca2+ channels with a minimal effect on depletion of internal Ca2+ stores.

Finally, gliotoxin induced intracellular production of superoxide possibly through a thiol redox cycling, which appeared to mediate suppressive effects on mast cell activation.

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