Effects of macrophage colony-stimulating factor (M-CSF) on anti-fungal activity of mononuclear phagocytes against Trichosporon asahii

Trichosporon asahii is an emerging opportunistic pathogen in immunocompromi sed patients. Little is known about the mechanisms of host defence against T. asahii. We investigated the fungicidal activity of human peripheral bloo d monocytes and murine peritoneal macrophages against T. asahii isolates, a nd the effects of M-CSF on the anti-fungal activity of mononuclear phagocyt es. We also established a neutropenic mouse model of disseminated trichospo ronosis with T. asahii. M-CSF enhanced the phagocytic fungicidal activity o f mononuclear cells, and infected mice treated with human M-CSF at 10 x 10( 6) U/kg showed a significant improvement in survival rate, with fewer funga l colony counts in the lung compared with control mice. Mice treated with h uman M-CSF showed higher concentrations of tumour necrosis factor-alpha (TN F-alpha) in the lung and plasma compared with control mice. The survival ra te was significantly reduced in mice treated with anti-mouse TNF-alpha. Our results showed that M-CSF enhanced the fungicidal activity of mononuclear phagocytes partly by production of TNF-alpha, and suggest that the administ ration of M-CSF to patients with disseminated trichosporonosis may be a use ful adjunct to conventional anti-microbial therapy and prophylaxis.