Mucosal administration of flagellin protects ...
Title :
Mucosal administration of flagellin protects mice from Streptococcus pneumoniae lung infection.
Author(s) :
Munoz, Natalia [Auteur]
Van Maele, Laurye [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Marqués, Juan [Auteur]
Rial, Analia [Auteur]
SIRARD, Jean-Claude [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Chabalgoity, Jose Alejandro [Auteur correspondant]
Van Maele, Laurye [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Marqués, Juan [Auteur]
Rial, Analia [Auteur]
SIRARD, Jean-Claude [Auteur]

Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Chabalgoity, Jose Alejandro [Auteur correspondant]
Journal title :
Infection and Immunity
Pages :
4226-4233
Publisher :
American Society for Microbiology
Publication date :
2010-07-19
ISSN :
0019-9567
English keyword(s) :
Chemokine
Epithelium
Flagellin
Lung inflammation
TLR5
Epithelium
Flagellin
Lung inflammation
TLR5
HAL domain(s) :
Sciences du Vivant [q-bio]/Immunologie
Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Maladies infectieuses
Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Maladies infectieuses
English abstract : [en]
Streptococcus pneumoniae is a major cause of pneumonia in infants and the elderly. Innate defenses are essential to control pneumococcal infections and deficient responses can trigger disease in susceptible individuals. ...
Show more >Streptococcus pneumoniae is a major cause of pneumonia in infants and the elderly. Innate defenses are essential to control pneumococcal infections and deficient responses can trigger disease in susceptible individuals. Here, we showed that flagellin can locally activate innate immunity and thereby increase the resistance to acute pneumonia. Flagellin mucosal treatment improved S. pneumoniae clearance in the lungs and promoted increased survival to infection. In addition, lung architecture was fully restored after the treatment of infected mice, indicating that flagellin allows the re-establishment of steady state conditions. Using a flagellin mutant that is unable to signal through TLR5, we established that TLR5 signaling is essential for protection. In the respiratory tract, flagellin induced neutrophil infiltration into airways and upregulated the expression of genes coding for IL-6, TNF-alpha, CXCL1, CXCL2 and CCL20. Using depleting antibodies, we demonstrated that neutrophils are major effectors for protection. Further, we found that B and T cell-deficient SCID mice clear S. pneumoniae challenge to the same extent than immunocompetent animals suggesting that these cell populations are not required for flagellin-induced protection. In conclusion, this study emphasizes that mucosal stimulation of innate immunity by a TLR not naturally engaged by S. pneumoniae can increase the potency to cure pneumococcal pneumonia.Show less >
Show more >Streptococcus pneumoniae is a major cause of pneumonia in infants and the elderly. Innate defenses are essential to control pneumococcal infections and deficient responses can trigger disease in susceptible individuals. Here, we showed that flagellin can locally activate innate immunity and thereby increase the resistance to acute pneumonia. Flagellin mucosal treatment improved S. pneumoniae clearance in the lungs and promoted increased survival to infection. In addition, lung architecture was fully restored after the treatment of infected mice, indicating that flagellin allows the re-establishment of steady state conditions. Using a flagellin mutant that is unable to signal through TLR5, we established that TLR5 signaling is essential for protection. In the respiratory tract, flagellin induced neutrophil infiltration into airways and upregulated the expression of genes coding for IL-6, TNF-alpha, CXCL1, CXCL2 and CCL20. Using depleting antibodies, we demonstrated that neutrophils are major effectors for protection. Further, we found that B and T cell-deficient SCID mice clear S. pneumoniae challenge to the same extent than immunocompetent animals suggesting that these cell populations are not required for flagellin-induced protection. In conclusion, this study emphasizes that mucosal stimulation of innate immunity by a TLR not naturally engaged by S. pneumoniae can increase the potency to cure pneumococcal pneumonia.Show less >
Language :
Anglais
Peer reviewed article :
Oui
Audience :
Internationale
Popular science :
Non
Source :
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