Neutrophil elastase mediates innate host protection against Pseudomonas aeruginosa

Tim O. Hirche, Rym Benabid, Gaetan Deslee, Sophie Gangloff, Samuel Achilefu, Moncef Guenounou, François Lebargy, Robert E. Hancock, Azzaq Belaaouaj

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4945-4954
Number of pages10
JournalJournal of Immunology
Volume181
Issue number7
DOIs
StatePublished - Oct 1 2008
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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