Previous studies have established that phagocytes are key cells of the pulmonary innate immune defense against A. fumigatus, an opportunistic fungus responsible of invasive pulmonary aspergillosis. Macrophages detect A. fumigatus via Toll-like receptors (TLR) 2 and 4, and respond by the MyD88-NF-B-dependent synthesis of inflammatory mediators. In the present study, we demonstrate that respiratory epithelial cells also sense A. fumigatus and participate to the host defense. Thus, the interaction of respiratory epithelial cells with germinating but not resting conidia of A. fumigatus results in interleukin (IL)-8 synthesis that is controlled by PI3 kinase, p38 MAPK and ERK1/2. Using MyD88-dominant negative transfected cells, we also show that IL-8 production is not dependent on the TLR-MyD88 pathway, although the MyD88 pathway is activated by A. fumigatus and leads to NF-B activation. Thus, our results provide evidence for the existence of two independent signalling pathways activated in respiratory epithelial cells by A. fumigatus, one which is MyD88 dependent and another that is My88 independent and involved in IL-8 synthesis.