Pseudomonas aeruginosa induces localized immunosuppression during pneumonia.
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.
Diaz
Maureen H
MH
Department of Microbiology/Immunology, Northwestern University, Chicago, Illinois, USA.
Shaver
Ciara M
CM
King
John D
JD
Musunuri
Srinidhi
S
Kazzaz
Jeffrey A
JA
Hauser
Alan R
AR
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000633:toxicity*; D002470:Cell Survival; D015169:Colony Count, Microbial; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007108:Immune Tolerance; D051379:Mice; D008807:Mice, Inbred BALB C; D016254:Mutagenesis, Insertional; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D010586:Phagocytes / Q000187:drug effects / Q000276:immunology; D010587:Phagocytosis; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000276:immunology* / Q000472:pathogenicity; D014774:Virulence
D001426:Bacterial Proteins; C111749:pseudomonas exoprotein A protein, Pseudomonas aeruginosa