期刊
CRITICAL CARE MEDICINE
卷 41, 期 9, 页码 E191-E199出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CCM.0b013e31828a25d6
关键词
alveolar macrophages; bacterial pneumonia; Candida albicans; interferon-gamma; phagocytosis; Pseudomonas aeruginosa
资金
- French Society of Intensive Care (SRLF)
- Societe de Pneumologie de Langue Francaise
- Fonds d'Etudes et de Recherche du Corps Medical des Hopitaux de Paris
- Legs Poix
- Pfizer
- French Society of Intensive Care
- INSERM
- Hood Foundation
- Hearst Foundation
- ANR
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. Design: Experimental animal investigation. Setting: University research laboratory. Subjects: Pathogen-free male Wistar rats weighing 250-275 g. Interventions: 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. Measurements and Main 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.
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