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


Journal

Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society
ISSN: 1873-5010
Titre abrégé: J Cyst Fibros
Pays: Netherlands
ID NLM: 101128966

Informations de publication

Date de publication:
03 2022
Historique:
received: 09 02 2021
revised: 07 06 2021
accepted: 04 08 2021
pubmed: 24 8 2021
medline: 14 4 2022
entrez: 23 8 2021
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 34420900
pii: S1569-1993(21)01343-6
doi: 10.1016/j.jcf.2021.08.002
pii:
doi:

Substances chimiques

Toll-Like Receptor 5 0
Cystic Fibrosis Transmembrane Conductance Regulator 126880-72-6
Flagellin 12777-81-0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e117-e121

Informations de copyright

Copyright © 2021. Published by Elsevier B.V.

Auteurs

Isabelle Fleurot (I)

INRAE, Université de Tours, UMR-1282 Infectiologie et Santé Publique (ISP), Centre de Recherche Val de Loire, 37380 Nouzilly, France.

Raquel López-Gálvez (R)

INRAE, Université de Tours, UMR-1282 Infectiologie et Santé Publique (ISP), Centre de Recherche Val de Loire, 37380 Nouzilly, France.

Pascal Barbry (P)

Université Côte d'Azur, CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, F06560 Sophia Antipolis, France.

Antoine Guillon (A)

Université de Tours, 37000 Tours, France; INSERM U1100, Centre d'étude des pathologies respiratoires (CEPR), 37000 Tours, France.

Mustapha Si-Tahar (M)

Université de Tours, 37000 Tours, France; INSERM U1100, Centre d'étude des pathologies respiratoires (CEPR), 37000 Tours, France.

Andrea Bähr (A)

CIMM-Gene Center and Center for Innovative Medical Models, LMU Munich, Germany.

Nikolai Klymiuk (N)

CIMM-Gene Center and Center for Innovative Medical Models, LMU Munich, Germany.

Jean-Claude 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.

Ignacio 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.

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Classifications MeSH