Pulmonary tissue resistance to Candida albicans in normal and in immunosuppressed mice

We characterized the clearance of Candida albicans from the lung using a murine model for pulmonary aspiration. Swiss Webster mice uniformly survived intratracheally administered boluses of C. albicans (1 to 30 X 10(5) colony-forming units of yeast) which killed the majority of mice (more than 85%) when injected intravenously. Clearance studies, using quantitative cultures of lung homogenates, demonstrated rapid elimination of C. albicans from the lung after a 6-h delay; the residual fractions of viable fungi were 8.3 and 0.7% of the initial inoculums at 24 and 48 h, respectively, after inoculation. The number of leukocytes in the bronchoalveolar spaces increased twofold to threefold after deposition, and this primarily reflected a neutrophil influx. Histologic studies supported the bronchoalveolar lavage results and revealed a diffuse interstitial neutrophilic infiltrate and clusters of inflammatory cells in air spaces at 6 and 24 h after Candida deposition. Examination of lavage pellets demonstrated that both neutrophils and macrophages ingested C. albicans in vivo. Immunosuppression (orally administered prednisolone for 2 wk) delayed the clearance of C. albicans from the lung. However, evaluation of neutrophil migration into bronchoalveolar spaces and of the in vivo ingestion capacity of both macrophages and neutrophils did not identify differences that could explain this delayed clearance in steroid-treated mice. The fungicidal activity of pulmonary leukocytes was measured with in vitro assays and was similar in phagocyte cultures from control and steroid-treated mice. In summary, intrinsic pulmonary defense factors and recruited neutrophils rapidly and completely clear C. albicans from the lung after bolus deposition.(ABSTRACT TRUNCATED AT 250 WORDS)