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Radioresistant cells expressing TLR5 control the respiratory epithelium's innate immune responses to flagellin.
Janot L., Sirard J.-C., Secher T., Noulin N., Fick L., Akira S., Uematsu S., Didierlaurent A., Hussell T., Ryffel B. et al
European Journal of Immunology 39, 6 (2009) 1587-96 - http://www.hal.inserm.fr/inserm-00385299
(19424969)
Radioresistant cells expressing TLR5 control the respiratory epithelium's innate immune responses to flagellin.
Laure Janot1, Jean-Claude Sirard () 2, Thomas Secher1, Nicolas Noulin1, Lizette Fick3, Shizuo Akira4, Satoshi Uematsu4, Arnaud Didierlaurent5, Tracy Hussell5, Bernhard Ryffel () 1, François Erard1
1 :  IEM - Immunologie et embryologie moléculaires
CNRS : UMR6218 – Université d'Orléans
3B rue de la Ferollerie 45071 ORLEANS CEDEX 2
France
2 :  Interactions cellulaires et moléculaires des bactéries pathogènes avec l'hôte
http://www.ibl.fr/e0364/e0364.htm
INSERM : U801 – Institut Pasteur de Lille – Université Lille II - Droit et santé
Institut de Biologie de Lille 1, Rue du Professeur Calmette 59021 LILLE CEDEX
France
3 :  Institute of Immunology and Infectious Disease and Molecular Medicine
Institute of Immunology and Infectious Disease and Molecular Medicine
University of Cape Town, Cape Town, South Africa
Afrique Du Sud
4 :  Department of Host Defense
Osaka University
Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
Japon
5 :  Kennedy Institute of Rheumatology
imperial College of London
Faculty of Medicine, London
Royaume-Uni
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.
Sciences du Vivant/Immunologie
Sciences du Vivant/Médecine humaine et pathologie/Maladies infectieuses
Anglais
0014-2980

Articles dans des revues avec comité de lecture
10.1002/eji.200838907
European Journal of Immunology (Eur J Immunol)
Publisher Wiley-VCH Verlag Berlin
ISSN 0014-2980 (eISSN : 1521-4141)
internationale
06/2009
07/05/2009
39
6
1587-96

Chemokine – Epithelium – Flagellin – Lung inflammation – TLR5
Animals – Humans – Immunity – Mucosal – Signal Transduction – Toll-Like Receptor 5 – Mucosal Tracts Infections – Flagellin – Neutrophil – Adaptor Proteins – Vesicular Transport – Administration – Intranasal – Animals – Bronchoalveolar Lavage Fluid – Bronchoconstriction – Cell Movement – Chemokines – Cytokines – Epithelial Cells – Gene Expression – Innate – Inflammation – Lung – Macrophages – Alveolar – Mice – Inbred C57BL – Knockout – Myeloid Differentiation Factor 88 – Neutrophils – Peroxidase – Plethysmography – Whole Body – Radiation Chimera – Radiation Tolerance – Respiratory Mucosa
French Ministry of Education European Community (STREP SavinMucoPath INCO-CT-2006-032296) Région Nord Pas de Calais (ARCir Europe) UK Medical Research Council
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