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 LD50, 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. Pneumonia caused by Pseudomonas aeruginosa is a ma-jor cause of morbidity and mortality among patients who require mechanical ventilation [1]. Death in these patients has been ascribed to a number of virulence factors, including the type III secreted exotoxins [2–4], phospholipase C [5], proteases [6], exotoxin A [7], an