Cytokine responses and regulation of interferon-gamma release by human mononuclear cells to Aspergillus fumigatus and other filamentous fungi.

There is substantial evidence that the production of proinflammatory cytokines is important in host resistance to invasive aspergillosis. Knowledge of the host response towards other filamentous fungi is scarce, as most studies have focused on Aspergillus fumigatus. In addition, interferon-gamma (IFNgamma) plays a crucial role in the control of invasive aspergillosis, but little is known about the regulation of IFNgamma after stimulation of mononuclear cells by A. fumigatus. Cytokine responses to four different Aspergillus spp., Scedosporium prolificans, and a Rhizopus oryzae strain were compared for their ability to induce the release of tumour necrosis factor-alpha (TNFalpha) and interleukin(IL)-6 by human monocytes. S. prolificans induced significantly more TNFalpha and IL-6 release compared to A. fumigatus, while the various Aspergillus spp. induce comparable levels of these cytokines. By using specific cytokine inhibitors we were able to show that endogenous IL-1, but not IL-18 and TNFalpha was required for IFNgamma and IL-10 release upon stimulation with A. fumigatus hyphae, whereas conidia induced IFNgamma stimulation is independent of these cytokines.