RGD Reference Report - Mucosal administration of flagellin protects mice from Streptococcus pneumoniae lung infection. - Rat Genome Database

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

Authors: Munoz, N  VAN Maele, L  Marques, JM  Rial, A  Sirard, JC  Chabalgoity, JA 
Citation: Munoz N, etal., Infect Immun. 2010 Jul 19.
RGD ID: 4143255
Pubmed: PMID:20643849   (View Abstract at PubMed)
PMCID: PMC2950348   (View Article at PubMed Central)
DOI: DOI:10.1128/IAI.00224-10   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IL6HumanPneumococcal Pneumonia  ISOIl6 (Mus musculus) RGD 
Il6RatPneumococcal Pneumonia  ISOIl6 (Mus musculus) RGD 
Il6MousePneumococcal Pneumonia  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il6  (interleukin 6)

Genes (Mus musculus)
Il6  (interleukin 6)

Genes (Homo sapiens)
IL6  (interleukin 6)


Additional Information