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European Journal of Immunology 39, 6 (2009) 1587-96
Radioresistant cells expressing TLR5 control the respiratory epithelium's innate immune responses to flagellin.
Laure Janot 1, Jean-Claude Sirard ( ) 2, Thomas Secher 1, Nicolas Noulin 1, Lizette Fick 3, Shizuo Akira 4, Satoshi Uematsu 4, Arnaud Didierlaurent 5, Tracy Hussell 5, Bernhard Ryffel ( ) 1, François Erard 1
(06/2009)

Bacterial products (such as endotoxins and flagellin) trigger innate immune responses through TLRs. Flagellin-induced signalling involves TLR5 and MyD88 and, according to some reports, TLR4. Whereas epithelial and dendritic cells are stimulated by flagellin in vitro, the cell contribution to the in vivo response is still unclear. Here, we studied the respective roles of radioresistant and radiosensitive cells in flagellin-induced airway inflammation in mice. We found that i.n. delivery of flagellin elicits a transient change in respiratory function and an acute, pro-inflammatory response in the lungs, characterized by TLR5- and MyD88-dependent chemokine secretion and neutrophil recruitment. In contrast, TLR4, CD14 and TRIF were not essential for flagellin-mediated responses, indicating that TLR4 does not cooperate with TLR5 in the lungs. Respiratory function, chemokine secretion and airway infiltration by neutrophils were dependent on radioresistant, TLR5-expressing cells. Furthermore, lung haematopoietic cells also responded to flagellin by activating TNF-alpha production. We suggest that the radioresistant lung epithelial cells are essential for initiating early, TLR5-dependent signalling in response to flagellin and thus triggering the lung's innate immune responses.
1 :  Immunologie et embryologie moléculaires (IEM)
CNRS : UMR6218 – Université d'Orléans
2 :  Interactions cellulaires et moléculaires des bactéries pathogènes avec l'hôte
INSERM : U801 – Institut Pasteur de Lille – Université Lille II - Droit et santé
3 :  Institute of Immunology and Infectious Disease and Molecular Medicine
Institute of Immunology and Infectious Disease and Molecular Medicine
4 :  Department of Host Defense
Osaka University
5 :  Kennedy Institute of Rheumatology
imperial College of London
Sciences du Vivant/Immunologie

Sciences du Vivant/Médecine humaine et pathologie/Maladies infectieuses
Chemokine – Epithelium – Flagellin – Lung inflammation – TLR5
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