Immunosuppressive substances in Aspergillus fumigatus culture filtrate

Invasive aspergillosis has become a serious problem in clinical practice, but the actual factor that confers virulence on the fungus has not been thoroughly elucidated. To identify and isolate the immunosuppressive substances produced by the fungus, the bioactivity of culture filtrates was assessed, and analyses of the culture filtrates were carried out. Culture filtrates from different strains of Aspergillus fumigatus were assessed for their effect on human polymorphonuclear leukocytes and murine macrophages. To assess their activities in vivo, their effect on the survival of mice infected by the fungus was also studied. Subsequently, the composition of the culture filtrates was analyzed by gas chromatography-mass spectrometry. The analyses revealed that the culture filtrates contained gliotoxin at concentrations of 3 to 4 microgram/ml, and some other unidentified compounds. The bioactivities of the culture filtrates were similar to those of gliotoxin. The fungal culture filtrate reduced the survival of infected mice, but the filtrate itself did not cause the death of mice. However, all the bioactivities could not be accounted for by gliotoxin itself. These results indicate that gliotoxin in the culture filtrates may be responsible for part of the immunosuppressive activity, but some other components produced by A. fumigatus contribute, in an additive or synergistic manner, to the virulence of the fungus.