期刊
JOURNAL OF IMMUNOLOGY
卷 181, 期 7, 页码 4945-4954出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.181.7.4945
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资金
- Conseil Regional Champagne-Ardenne
- Institut National de la Sante et de la Recherche Medicale
- Programme Avenir
- Fondation pour la Recherche Medicale
- Agence Nationale de la Recherche
- Canadian Institutes of Health Research
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.
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