Legionella species are Gram-negative bacteria that can induce a rare but severe form of pneumonia, known as Legionnaire’s disease. IL-18, mainly produced by macrophages, protects against a variety of pathogens by promoting IFN-g production by T and NK cells which, in turn, activates microbiocidal mechanisms in myeloid cells. Surprisingly, we show that defense against Legionella longbeachae, the globally second most prevalent Legionella spp., requires expression of the IL-18R on stromal cells, rather than on lymphocytes, indicating a novel pathway of IL-18-induced protection. Using mouse genetics, spectral confocal microscopy, correlated light and electron microscopy (CLEM), multicolor flowcytometry and standard microbiology techniques, we gained results suggesting that IL-18R expression by bronchial ciliated epithelial cells may promote neutrophil-mediated killing of L. longbeachae. On the other hand, epithelial cell autonomous defense mechanisms, like mucociliary clearance, do apparently not play a role in this novel pathway. We are currently investigating the molecular mechanisms by which IL-18R+ ciliated epithelial cells promote neutrophil microbiocidal capacity using organotypic cell culture systems, like air liquid interface culture and organoids, as well as proteomic and RNAsequencing approaches.