Abstract
Aspergillus fumigatus is a human pathogen, able to cause invasive aspergillosis in immunosuppressed patients. In the immunocompetent situation inhaled conidia are easily cleared by the immune system. Knowledge of the cellular pathways involved in the innate immunity against A. fumigatus is poorly represented. Therefore, we aimed to investigate the immune response against A. fumigatus in murine alveolar macrophages in terms of MAP kinases, NF-kappaB and cytokine signalling. Our investigations revealed that in murine alveolar macrophages, MAP kinases, ERK and p38 are activated under in vitro conditions, following addition of A. fumigatus conidia. In vivo experiments, however, showed that only ERK is directly involved, because activation of p38 was negligible. Immunosuppression with corticosteroids inhibited phosphorylation of ERK and was directly accompanied with a strongly decreased level of TNF-alpha and additional cytokines. In addition, killing of A. fumigatus conidia is reduced using the ERK inhibitor. Therefore, ERK appears to be an essential MAP kinase in the defence against A. fumigatus. Activation of the transcription factor NFkappaB appeared only at late times after infection suggesting an association with the intracellular swelling of conidia.