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Article Dans Une Revue American Journal of Respiratory Cell and Molecular Biology Année : 2021

Airway administration of flagellin regulates the inflammatory response to Pseudomonas aeruginosa

Raquel López-Gálvez
Isabelle Fleurot
Sascha Trapp
Olivier Michel
Claire Chevaleyre
  • Fonction : Auteur
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Céline Barc
Mickael Riou
Tobias May
  • Fonction : Auteur

Résumé

Excessive lung inflammation and airway epithelium damage are hallmarks of human inflammatory lung diseases, such as cystic fibrosis (CF). Enhancement of innate immunity provides protection against pathogens while reducing lung-damaging inflammation. However, the mechanisms underlying innate immunity-mediated protection in the lung remain mysterious, in part because of the lack of appropriate animal models for these human diseases. Toll-like receptor 5 (TLR5) stimulation by its specific ligand, the bacterial protein flagellin, has been proposed to enhance protection against several respiratory infectious diseases, although other cellular events, such as calcium signaling, may also control the intensity of innate immune response. Here, we investigated the molecular events prompted by stimulation with flagellin and its role in regulating innate immunity in the lung of the pig, which is anatomically and genetically more similar to humans than rodent models. We found that flagellin treatment modulated NF-κB signaling and intracellular calcium homeostasis in airway epithelial cells. 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 the inflammatory response in inflammatory lung diseases such as CF.
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Dates et versions

hal-03258174 , version 1 (20-10-2021)

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Paternité - Pas d'utilisation commerciale - Pas de modification

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Raquel López-Gálvez, Isabelle Fleurot, Pablo Chamero, Sascha Trapp, Olivier Michel, et al.. Airway administration of flagellin regulates the inflammatory response to Pseudomonas aeruginosa. American Journal of Respiratory Cell and Molecular Biology, 2021, 65 (4), pp.378-389. ⟨10.1165/rcmb.2021-0125OC⟩. ⟨hal-03258174⟩
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