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Neutrophil elastase targets virulence factors of enterobacteria

Author

Listed:
  • Yvette Weinrauch

    (New York University School of Medicine)

  • Doreen Drujan

    (New York University School of Medicine)

  • Steven D. Shapiro

    (Brigham and Women's Hospital, Harvard Medical School)

  • Jerrold Weiss

    (University of Iowa College of Medicine, Iowa City Veterans' Administration Medical Center)

  • Arturo Zychlinsky

    (New York University School of Medicine
    Max Planck Institute for Infection Biology)

Abstract

Shigellae cause bacillary dysentery, a bloody form of diarrhoea that affects almost 200 million people and causes nearly 2 million deaths per year1. Shigella invades the colonic mucosa, where it initiates an acute inflammation, rich in neutrophils, that initially contributes to tissue damage and eventually resolves the infection2. Neutrophils are phagocytic cells that kill microorganisms3,4 but it is unclear how neutrophils control pathogenic bacteria expressing virulence factors that manipulate host cells. In contrast to other cells, neutrophils prevent the escape of Shigella from phagocytic vacuoles in which the bacteria are killed5. Here we identify human neutrophil elastase (NE) as a key host defence protein: NE degrades Shigella virulence factors at a 1,000-fold lower concentration than that needed to degrade other bacterial proteins. In neutrophils in which NE is inactivated pharmacologically or genetically, Shigella escapes from phagosomes, increasing bacterial survival. NE also preferentially cleaves virulence factors of Salmonella and Yersinia. These findings establish NE as the first neutrophil factor that targets bacterial virulence proteins.

Suggested Citation

  • Yvette Weinrauch & Doreen Drujan & Steven D. Shapiro & Jerrold Weiss & Arturo Zychlinsky, 2002. "Neutrophil elastase targets virulence factors of enterobacteria," Nature, Nature, vol. 417(6884), pages 91-94, May.
  • Handle: RePEc:nat:nature:v:417:y:2002:i:6884:d:10.1038_417091a
    DOI: 10.1038/417091a
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    Cited by:

    1. Benjamin T. Kopp & Juan Antonio Ortega-GarcĂ­a & S. Christy Sadreameli & Jack Wellmerling & Estelle Cormet-Boyaka & Rohan Thompson & Sharon McGrath-Morrow & Judith A. Groner, 2016. "The Impact of Secondhand Smoke Exposure on Children with Cystic Fibrosis: A Review," IJERPH, MDPI, vol. 13(10), pages 1-10, October.

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