title: Response of CFTR-deficient mice to long-term chronic Pseudomonas aeruginosa infection and PTX3 therapy.
abstract: BACKGROUND
  In cystic fibrosis (CF) patients, chronic lung infection and inflammation due to Pseudomonas aeruginosa contribute to the decline of lung function. The increased prevalence of multidrug resistance among bacteria and the adverse effects of antiinflammatory agents highlight the need for alternative therapeutic approaches that should be tested in a relevant animal model.
  
  
  METHODS
  Gut-corrected CF and non-CF mice were chronically infected with a multidrug-resistant P. aeruginosa strain and treated with the long pentraxin PTX3. Body weight, bacterial count, inflammation, and lung pathology were evaluated after 12 days. PTX3 localization in CF sputum specimens was analyzed by immunofluorescence.
  
  
  RESULTS
  Chronic P. aeruginosa infection developed similarly in CF and non-CF mice but differed in terms of the inflammatory response. Leukocyte recruitment in the airways, cytokine levels, and chemokine levels were significantly higher in CF mice, compared with non-CF mice. PTX3 treatment, which facilitates phagocytosis of pathogens, reduced P. aeruginosa colonization and restored airway inflammation in CF mice to levels observed in non-CF mice. The presence of PTX3 in CF sputum, in leukocytes, or bound to P. aeruginosa macrocolonies, as well as previous data on PTX3 polymorphisms in colonized CF patients, confirm the relevance of this molecule.
  
  
  CONCLUSIONS
  These findings represent a step forward in demonstrating the therapeutic potential of PTX3 in CF.
authors.affiliation: Infection and Cystic Fibrosis Unit, Division of Immunology, Transplantation, and Infectious Diseases, San Raffaele Scientific Institute, Via Olgettina 58, Milan, Italy.
authors.forename: Moira
authors.initials: M
authors.lastname: Paroni
authors.forename: Federica
authors.initials: F
authors.lastname: Moalli
authors.forename: Manuela
authors.initials: M
authors.lastname: Nebuloni
authors.forename: Fabio
authors.initials: F
authors.lastname: Pasqualini
authors.forename: Tracey
authors.initials: T
authors.lastname: Bonfield
authors.forename: Alessandro
authors.initials: A
authors.lastname: Nonis
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
authors.forename: Cecilia
authors.initials: C
authors.lastname: Garlanda
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bragonzi
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000627:therapeutic use*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D018181:Mice, Inbred CFTR / Q000276:immunology / Q000382:microbiology*; D010587:Phagocytosis / Q000276:immunology; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D011994:Recombinant Proteins / Q000627:therapeutic use; D000683:Serum Amyloid P-Component / Q000627:therapeutic use*; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D011994:Recombinant Proteins; D000683:Serum Amyloid P-Component; D000099153:Pentraxins
keywords: Cystic Fibrosis; Mouse Model; PTX3; Pseudomonas Infection; Respiratory Tract Infections; inflammation