• Damien Roux, Stéphane Gaudry, Linda Khoy-Ear, Meryem Aloulou, Mathilde Phillips-Houlbracq, Julie Bex, David Skurnik, Erick Denamur, Renato C Monteiro, Didier Dreyfuss, and Jean-Damien Ricard.
• Institut National de la Santé et de la Recherche Médicale, INSERM U722, Paris, France.
• Crit. Care Med. 2013 Sep 1; 41 (9): e191-9.

ObjectiveTo 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.DesignExperimental animal investigation.SettingUniversity research laboratory.SubjectsPathogen-free male Wistar rats weighing 250-275 g.InterventionsRats 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.Measurements And Main ResultsC. 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.ConclusionsC. 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.

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