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Flagellin pre-treatment reduced the NF-κB nuclear translocation and the expression of pro-inflammatory cytokines to a second flagellin stimulus as well as to Pseudomonas aeruginosa infection. Moreover, in vivo administration of flagellin decreased the severity of P. aeruginosa-induced pneumonia. Then, we confirmed these beneficial effects of flagellin in a pathological model of CF by using ex vivo precision-cut lung slices from a CF pig model. These results provide evidence that flagellin treatment contribute to a better regulation of