title: Airway fungal colonization compromises the immune system allowing bacterial pneumonia to prevail.
abstract: OBJECTIVE
  To study the correlation between fungal colonization and bacterial pneumonia and to test the effect of antifungal treatments on the development of bacterial pneumonia in colonized rats.
  
  
  METHODS
  Experimental animal investigation.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Pathogen-free male Wistar rats weighing 250-275 g.
  
  
  METHODS
  Rats were colonized by intratracheal instillation of Candida albicans. Fungal clearance from the lungs and immune response were measured. Both colonized and noncolonized animals were secondarily instilled with different bacterial species (Pseudomonas aeruginosa, Escherichia coli, or Staphylococcus aureus). Bacterial phagocytosis by alveolar macrophages was evaluated in the presence of interferon-gamma, the main cytokine produced during fungal colonization. The effect of antifungal treatments on fungal colonization and its immune response were assessed. The prevalence of P. aeruginosa pneumonia was compared in antifungal treated and control colonized rats.
  
  
  RESULTS
  C. albicans was slowly cleared and induced a Th1-Th17 immune response with very high interferon-gamma concentrations. Airway fungal colonization favored the development of bacterial pneumonia. Interferon-gamma was able to inhibit the phagocytosis of unopsonized bacteria by alveolar macrophages. Antifungal treatment decreased airway fungal colonization, lung interferon-gamma levels and, consequently, the prevalence of subsequent bacterial pneumonia.
  
  
  CONCLUSIONS
  C. albicans airway colonization elicited a Th1-Th17 immune response that favored the development of bacterial pneumonia via the inhibition of bacterial phagocytosis by alveolar macrophages. Antifungal treatment decreased the risk of bacterial pneumonia in colonized rats.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, INSERM U722, Paris, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Roux
authors.forename: Stéphane
authors.initials: S
authors.lastname: Gaudry
authors.forename: Linda
authors.initials: L
authors.lastname: Khoy-Ear
authors.forename: Meryem
authors.initials: M
authors.lastname: Aloulou
authors.forename: Mathilde
authors.initials: M
authors.lastname: Phillips-Houlbracq
authors.forename: Julie
authors.initials: J
authors.lastname: Bex
authors.forename: David
authors.initials: D
authors.lastname: Skurnik
authors.forename: Erick
authors.initials: E
authors.lastname: Denamur
authors.forename: Renato C
authors.initials: RC
authors.lastname: Monteiro
authors.forename: Didier
authors.initials: D
authors.lastname: Dreyfuss
authors.forename: Jean-Damien
authors.initials: JD
authors.lastname: Ricard
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D001980:Bronchi / Q000382:microbiology*; D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development*; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000382:microbiology; D008297:Male; D010587:Phagocytosis / Q000187:drug effects; D018410:Pneumonia, Bacterial / Q000188:drug therapy / Q000382:microbiology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000935:Antifungal Agents; D007371:Interferon-gamma