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Mucosal administration of flagellin protects mice from Streptococcus pneumoniae lung infection.

Abstract : 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.
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Contributor : Jean-Claude Sirard Connect in order to contact the contributor
Submitted on : Wednesday, September 22, 2010 - 3:35:54 PM
Last modification on : Wednesday, March 23, 2022 - 3:51:02 PM
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Natalia Munoz, Laurye van Maele, Juan Marqués, Analia Rial, Jean-Claude Sirard, et al.. Mucosal administration of flagellin protects mice from Streptococcus pneumoniae lung infection.. Infection and Immunity, American Society for Microbiology, 2010, 78 (10), pp.4226-4233. ⟨10.1128/IAI.00224-10⟩. ⟨inserm-00520159⟩



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