Pseudomonas aeruginosa induces localized immunosuppression during pneumonia

Maureen H. Diaz, Ciara M. Shaver, John D. King, Srinidhi Musunuri, Jeffrey A. Kazzaz, Alan R. Hauser

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

Hospital-acquired bacterial pneumonia is a common and serious complication of modern medical care. Many aspects of such infections remain unclear, including the mechanisms by which invading pathogens resist clearance by the innate immune response and the tendency of the infections to be polymicrobial. Here, we used a mouse model of infection to show that Pseudomonas aeruginosa, a leading cause of hospital-acquired pneumonia, interferes with the ability of recruited phagocytic cells to eradicate bacteria from the lung. Early in infection, phagocytic cells, predominantly neutrophils, are recruited to the lungs but are incapacitated when they enter the airways by the P. aeruginosa toxin ExoU. The resulting paucity of functioning phagocytes allows P. aeruginosa to persist within the lungs and results in local immunosuppression that facilitates superinfection with less-pathogenic bacteria. Together, our results provide explanations for previous reports linking ExoU-secreting P. aeruginosa with more severe pulmonary infections and for the tendency of hospital-acquired pneumonia to be polymicrobial.

Original languageEnglish (US)
Pages (from-to)4414-4421
Number of pages8
JournalInfection and immunity
Volume76
Issue number10
DOIs
StatePublished - Oct 2008

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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