학술논문

TLR5 signalling is hyper-responsive in porcine cystic fibrosis airways epithelium.
Document Type
Academic Journal
Author
Fleurot I; INRAE, Université de Tours, UMR-1282 Infectiologie et Santé Publique (ISP), Centre de Recherche Val de Loire, 37380 Nouzilly, France.; López-Gálvez R; INRAE, Université de Tours, UMR-1282 Infectiologie et Santé Publique (ISP), Centre de Recherche Val de Loire, 37380 Nouzilly, France.; Barbry P; Université Côte d'Azur, CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, F06560 Sophia Antipolis, France.; Guillon A; Université de Tours, 37000 Tours, France; INSERM U1100, Centre d'étude des pathologies respiratoires (CEPR), 37000 Tours, France.; Si-Tahar M; Université de Tours, 37000 Tours, France; INSERM U1100, Centre d'étude des pathologies respiratoires (CEPR), 37000 Tours, France.; Bähr A; CIMM-Gene Center and Center for Innovative Medical Models, LMU Munich, Germany.; Klymiuk N; CIMM-Gene Center and Center for Innovative Medical Models, LMU Munich, Germany.; Sirard JC; Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR9017 - CIIL - Center for Infection and Immunity of Lille, F-59000 Lille, France.; Caballero I; INRAE, Université de Tours, UMR-1282 Infectiologie et Santé Publique (ISP), Centre de Recherche Val de Loire, 37380 Nouzilly, France. Electronic address: ignacio.caballero-posadas@inrae.fr.
Source
Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101128966 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-5010 (Electronic) Linking ISSN: 15691993 NLM ISO Abbreviation: J Cyst Fibros Subsets: MEDLINE
Subject
Language
English
Abstract
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.
(Copyright © 2021. Published by Elsevier B.V.)