IN-VIVO IMMUNOSUPPRESSIVE ACTIVITY OF GLIOTOXIN, A METABOLITE PRODUCED BY HUMAN PATHOGENIC FUNGI

Aspergillosis is a disease caused by the opportunistic pathogen Asperg illus fumigatus and other related fungi. It occurs mainly in immunosup pressed people and causes very high mortality rates. A. fumigatus and other pathogenic fungi have been shown to produce a metabolite, glioto xin, which has immunosuppressive properties in vitro, but little is kn own about its in vivo activity. Here we report that gliotoxin has incr eased toxicity in mice after irradiation. A single injection of glioto xin delayed the recovery of immune cells after immunosuppression by su blethal irradiation by 2 weeks. Study of the morphology of cells of th e thymus, spleen, and mesenteric lymph nodes by light microscopy and e lectron microscopy and agarose gel electrophoresis of DNA from these o rgans showed that the injection of gliotoxin induced apoptosis in cell s of the immune system in vivo. Thus, gliotoxin does have immunosuppre ssive activity in vivo and could potentially play a significant role i n the pathogenesis of aspergillosis and other fungal diseases.