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TLR5 signalling is hyper-responsive in porcine cystic fibrosis airways epithelium

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Fleurot, Isabelle | López-Gálvez, Raquel | Barbry, Pascal | Guillon, Antoine | Si-Tahar, Mustapha | Bähr, Andrea | Klymiuk, Nikolai | Sirard, Jean-Claude | Caballero, Ignacio

Edité par CCSD ; Elsevier -

International audience. Excessive lung inflammation and airway epithelium damage are hallmarks of cystic fibrosis (CF) disease. It is unclear whether lung inflammation is related to an intrinsic defect in the immune response or to chronic infection. We aimed to determine whether TLR5-mediated response is defective in the CF airway epithelium. We used a newborn CF pig model to study intrinsic alterations in CF airway epithelium innate immune response. Airway epithelial cells (AECs) were stimulated with flagellin or lipopolysaccharide to determine responses specific for TLR5 and TLR4, respectively. We observed a significant increase in cytokine secretion when CF AECs were stimulated with flagellin compared to wild type (WT) AECs. These results were recapitulated when AECs were treated with an inhibitor of CFTR channel activity. We show that TLR5-signalling is altered in CF lung epithelium at birth. Modulation of TLR5 signalling could contribute to better control the excessive inflammatory response observed in CF lungs.

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