The role of flagellin versus motility in acute lung disease caused by Pseudomonas aeruginosa.
The flagellum of Pseudomonas aeruginosa has been implicated in acute pneumonia, and its flagellin is known to cause lung inflammation. However, its proinflammatory role, versus its motility function, as a cause of death by a whole bacterium has not been demonstrated. This issue was examined in a lung model of acute infection using different flagellar mutants. We found that the absence of motility does not significantly alter the LD(50), whereas the production of excess amounts of flagellin lowers it and results in early death. Next, we found that the absence of the Toll-like receptor 5 (TLR5) ligand, flagellin, results in slower clearance of this organism from the lungs and a delay in the time to death. These findings demonstrate the dual role of flagellin in host defense and in disease and suggest that the death in this model may be biphasic with flagellin playing a role early in the disease.
Balloy
Viviane
V
Institut Pasteur, Unité de Défense Innée et Inflammation, and INSERM U874, Paris, France.
Verma
Amrisha
A
Kuravi
Sudha
S
Si-Tahar
Mustapha
M
Chignard
Michel
M
Ramphal
Reuben
R
D000208:Acute Disease; D000818:Animals; D004195:Disease Models, Animal; D005408:Flagellin / Q000235:genetics / Q000276:immunology*; D007249:Inflammation; D007928:Lethal Dose 50; D051379:Mice; D008969:Molecular Sequence Data; D050505:Mutant Proteins; D011014:Pneumonia / Q000382:microbiology*; D011552:Pseudomonas Infections / Q000276:immunology* / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity*; D016019:Survival Analysis; D014774:Virulence
D050505:Mutant Proteins; D005408:Flagellin