title: Depletion of natural killer cells increases mice susceptibility in a Pseudomonas aeruginosa pneumonia model.
abstract: OBJECTIVE
  Pseudomonas aeruginosa infection is a clinically relevant infection involved in pneumonia in ICUs. Understanding the type of immune response initiated by the host during pneumonia would help defining new strategies to interfere with the bacteria pathogenicity. In this setting, the role of natural killer cells remains controversial. We assessed the role of systemic natural killer cells in a Pseudomonas aeruginosa mouse pneumonia model.
  
  
  METHODS
  Experimental study.
  
  
  METHODS
  Research laboratory from a university hospital.
  
  
  METHODS
  RjOrl:SWISS and BALB/cJ mice (weight, 20-24 g).
  
  
  METHODS
  Lung injuries were assessed by bacterial load, myeloperoxidase activity, endothelial permeability (pulmonary edema), immune cell infiltrate (histological analysis), proinflammatory cytokine release, and Ly6-G immunohistochemistry. Bacterial loads were assessed in the lungs and spleen. Natural killer cell number and status were assessed in spleen (flow cytometry and quantitative polymerase chain reaction). Depletion of natural killer cells was achieved through an IV anti-asialo-GM1 antibody injection.
  
  
  RESULTS
  Pseudomonas aeruginosa tracheal instillation led to an acute pneumonia with a rapid decrease of bacterial load in lungs and with an increase of endothelial permeability, proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β), and myeloperoxidase activity followed by Ly6-G positive cell infiltrate in lungs. Pseudomonas aeruginosa was detected in the spleen. Membrane markers of activation and maturation (CD69 and KLRG1 molecules) were increased in splenic natural killer cells during Pseudomonas aeruginosa infection. Splenic natural killer cells activated upon Pseudomonas aeruginosa infection produced interferon-γ but not interleukin-10. Ultimately, mice depleted of natural killer cells displayed an increased neutrophil numbers in the lungs and an increased mortality rate without bacterial load modifications in the lungs, indicating that mice depleted of natural killer cells were much more susceptible to infection compared with control animals.
  
  
  CONCLUSIONS
  We report for the first time that natural killer cells play a major role in the mice susceptibility toward a Pseudomonas aeruginosa-induced acute pneumonia model.
authors.affiliation: 1Laboratoire UPRES EA3826, Thérapeutiques Cliniques et Expérimentales des Infections, Faculté de Médecine, Université de Nantes, Nantes, France. 2CHU Nantes, Pôle Anesthésie Réanimations, Service d'Anesthésie Réanimation Chirurgicale, Hôtel Dieu, Nantes, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Broquet
authors.forename: Antoine
authors.initials: A
authors.lastname: Roquilly
authors.forename: Cédric
authors.initials: C
authors.lastname: Jacqueline
authors.forename: Gilles
authors.initials: G
authors.lastname: Potel
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Caillon
authors.forename: Karim
authors.initials: K
authors.lastname: Asehnoune
mesh_terms: D000818:Animals; D002469:Cell Separation; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008168:Lung / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D009504:Neutrophils / Q000378:metabolism*; D009195:Peroxidase / Q000032:analysis; D011552:Pseudomonas Infections / Q000276:immunology* / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity; D013154:Spleen / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D009195:Peroxidase