Experimental pulmonary candidiasis.
The initial interaction of Candida albicans with pulmonary tissue of B6D2/F1 mice was investigated. The LD50 for mice challenged intravenously (IV) was approximately 3 X 10(5) yeasts, whereas the LD50 by the intratracheal (IT) route was in excess of 10(8) yeasts. Mice challenged IV died of progressive yeast growth in the kidneys. In contrast, mice challenged IT rapidly eliminated the entire inoculum by the first day after challenge. Resident pulmonary alveolar macrophages (PAM) killed upwards of 70% of C. albicans in an in vitro killing assay. At effector: target ratios favoring the effector cell population resident PAM were able to restrict the formation of yeast germ tubes to only 30% of the yeasts, whereas at equivalent ratios virtually all of the intracellular yeasts produced germ tubes. Evaluation of the ability of PAM, harvested from genetically different strains of inbred mice, to kill C. albicans in vitro showed that killing ability was a property of resident PAM from mice with the black 6 background. It was discovered that during the initial stages of infection in vivo, the expression of the F4/80 surface molecule was down regulated, and the expression of the Mac 1 surface molecule upregulated. There were no quantitative changes in expression of either Mac 2, Mac 3, Ly 5 or the 5C6 surface epitopes. Taken together, the data show that pulmonary tissue is quantitatively very resistant to C. albicans infection, because of the ability of resident PAM to rapidly phagocytize and kill yeasts. Killing of C. albicans by resident PAM may be a property of a subset of this mononuclear phagocyte population and was accompanied by alterations in the expression of surface molecules.
Sawyer
R T
RT
Trudeau Institute, Saranac Lake, NY 12983.
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology*; D002452:Cell Count; D005434:Flow Cytometry; D007668:Kidney / Q000382:microbiology; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000276:immunology / Q000382:microbiology*; D008172:Lung Diseases, Fungal / Q000276:immunology*; D008264:Macrophages / Q000382:microbiology*; D051379:Mice; D008815:Mice, Inbred Strains; D010587:Phagocytosis; D013154:Spleen / Q000382:microbiology