Exacerbation of invasive aspergillosis by the immunosuppressive fungal metabolite, gliotoxin.
Invasive aspergillosis is a significant cause of death in immunocompromised individuals. The majority of strains of the main causative agent, Aspergillus fumigatus, produce gliotoxin, a secondary metabolite with demonstrated in vitro immunosuppressive activity. Pretreatment of normally resistant mice with a single injection of a sublethal dose of gliotoxin was sufficient to make them susceptible to infection and subsequent death, after challenge with A. fumigatus spores. Animals infected with the non-gliotoxin producing strain survived significantly longer than those infected with a gliotoxin producer. We propose that the release of gliotoxin by A. fumigatus hyphae during infection can exacerbate the pathogenesis of aspergillosis.
Sutton
P
P
Division of Immunology and Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia.
Waring
P
P
Müllbacher
A
A
D000818:Animals; D017209:Apoptosis; D001228:Aspergillosis / Q000209:etiology*; D001232:Aspergillus fumigatus / Q000378:metabolism*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005912:Gliotoxin / Q000096:biosynthesis / Q000633:toxicity*; D007166:Immunosuppressive Agents / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects
D007166:Immunosuppressive Agents; D005912:Gliotoxin