Neutrophil Elastase Mediates Innate Host Protection against Pseudomonas aeruginosa

According to the widely accepted view, neutrophil elastase (NE), a neutrophil-specific serine protease, is a major contributor to Pseudomonas aeruginosa infection-associated host tissue inflammation and damage, which in severe cases can lead to death. Herein, we provide for the first time compelling...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2008-10, Vol.181 (7), p.4945-4954
Main Authors: Hirche, Tim O, Benabid, Rym, Deslee, Gaetan, Gangloff, Sophie, Achilefu, Samuel, Guenounou, Moncef, Lebargy, Francois, Hancock, Robert E, Belaaouaj, Azzaq
Format: Article
Language:English
Subjects:
Animals
Bacterial Outer Membrane Proteins - genetics
Bacterial Outer Membrane Proteins - physiology
Disease Models, Animal
Genetic Predisposition to Disease
Immunity, Innate - genetics
Leukocyte Elastase - antagonists & inhibitors
Leukocyte Elastase - deficiency
Leukocyte Elastase - genetics
Leukocyte Elastase - physiology
Mice
Mice, Inbred C57BL
Mice, Knockout
Mutation
Pneumonia, Bacterial - enzymology
Pneumonia, Bacterial - immunology
Pneumonia, Bacterial - microbiology
Pseudomonas aeruginosa - chemistry
Pseudomonas aeruginosa - genetics
Pseudomonas aeruginosa - immunology
Pseudomonas Infections - enzymology
Pseudomonas Infections - immunology
Pseudomonas Infections - microbiology
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Summary:According to the widely accepted view, neutrophil elastase (NE), a neutrophil-specific serine protease, is a major contributor to Pseudomonas aeruginosa infection-associated host tissue inflammation and damage, which in severe cases can lead to death. Herein, we provide for the first time compelling evidence that the host rather employs NE to protect itself against P. aeruginosa infection. Using a clinically relevant model of pneumonia, targeted deficiency in NE increased the susceptibility of mice to P. aeruginosa. We found that NE was required for maximal intracellular killing of P. aeruginosa by neutrophils. In investigating the mechanism of NE-mediated killing of P. aeruginosa, we found that NE degraded the major outer membrane protein F, a protein with important functions, including porin activity, maintenance of structural integrity, and sensing of host immune system activation. Consistent with this, the use of an isogenic mutant deficient in outer membrane protein F negated the role of NE in host defense against P. aeruginosa infection.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.181.7.4945